Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders.

BACKGROUND: One of the most consistent findings in schizophrenia research over the past decade is a reduction in the amplitude of an auditory event-related brain potential known as mismatch negativity (MMN), which is generated whenever a deviant sound occurs in a background of repetitive auditory stimulation. The reduced amplitude of MMN in schizophrenia was first observed for deviant sounds that differ in duration relative to background standard sounds, and similar findings have been observed for sounds that are deviant in frequency. The aim of this study was to determine whether first-degree relatives of schizophrenia patients show a similar reduction in MMN amplitude to duration deviants. METHODS: We measured MMN to duration increments (deviants 100 msec vs. standards 50 msec) in 22 medicated patients with a diagnosis in the schizophrenia spectrum, 17 individuals who were first-degree unaffected relatives of patients, and 21 healthy control subjects. RESULTS: Mismatch negativity amplitude was reduced in patients and relatives compared with control subjects. There were no significant differences between patients and relatives. In contrast, the subsequent positive component, P3a, was larger in relatives compared with patients. CONCLUSIONS: These findings suggest that a reduced MMN amplitude may be an endophenotype marker of the predisposition to schizophrenia.     

Temporal integration of deviant sound in automatic detection reflected by mismatch negativity

Mismatch negativity (MMN) is an event-related potential that is elicited by deviant sounds that are presented along with frequent sounds in the absence of attention. Auditory MMN is generated by the comparison process between sensory memory trace of a frequent auditory event and a deviant event. It is well known that frequent sounds are encoded in memory trace and processed as a single unit within 160-170 ms. This study examined whether deviant sound would be similarly processed as a temporal unit. Twelve healthy men were presented with relatively short standard sounds and relatively long deviant sounds that contained an omitted (i.e. silent) part. Three types of deviant sounds were designed to vary in duration. The MMN amplitude was gradually enhanced from the short to long duration deviant events that contained an omitted part. In contrast, MMN latency showed no significant differences among the deviants. These findings show that deviant sounds are also processed as a unitary event.     

The right profile: mismatch negativity in schizophrenia with and without auditory hallucinations as measured by a multi-feature paradigm.

ObjectiveTo examine pre-attentive acoustic change detection in schizophrenia patients with and without auditory hallucinations via mismatch negativity (MMN) extracted from a multi-feature paradigm.MethodsThis study examined the electroencephalograph (EEG)-derived MMN, recorded across 32 sites, in 12 hallucinating patients (HPs) with schizophrenia, 12 non-hallucinating patients (NPs) with schizophrenia and 12 healthy controls (HCs). MMN was recorded in response to a multi-feature MMN paradigm [Näätänen, R., et al., 2004. The mismatch negativity (MMN): towards the optimal paradigm. Clin. Neurophys. 115, 140–144] which employs frequency, duration, intensity, location and gap deviants. Differences in source localization were probed using standardized low resolution brain electromagnetic tomography (sLORETA).ResultsHPs showed significantly smaller MMNs to duration deviants compared to HCs and NPs, as well as smaller MMNs to intensity deviants compared to HCs. Regionalized differences between HCs and each of the patient groups were observed in response to frequency deviants. There were no significant group effects for location or gap deviants, or for MMN latency. Source localization using sLORETA showed no significant differences in MMN generator location across groups for any of the deviant stimuli.ConclusionsThe often-reported robust MMN deficit to duration deviants may be specific to schizophrenia patients afflicted with auditory hallucinations. Furthermore, by using symptom-specific groups, novel deficits of pre-attentive auditory processing, such as that observed to intensity deviants in HPs, may be revealed.SignificanceThe differential responding observed between both groups of patients with schizophrenia has implications for automatic processing within the auditory cortex of hallucinating patients and suggests that care must be taken when recruiting participants in studies involving schizophrenia to ensure consistent, replicable results.     

Changes in the duration and frequency of deviant stimuli engender different mismatch negativity patterns in temporal lobe epilepsy

Mismatch negativity (MMN) is an event-related potential (ERP) component that reflects preattentive sensory memory functions. Previous research revealed that MMN is generated by distinct sources in the frontal and temporal lobes. Event-related potential abnormalities have been shown in the vicinity of seizure foci in epilepsy. Additionally, no published study has investigated the MMN in response to variations in both frequency and duration deviants in patients with temporal lobe epilepsy (TLE). The aims of this study were to compare MMN changes between the frontocentral sites and the mastoid sites and to compare MMNs related to deviant stimuli with different durations and frequencies in patients with TLE. We recorded MMNs elicited by duration and frequency changes of deviant stimuli from 15 patients with TLE and 15 healthy control subjects. We found that mean MMN amplitudes related to duration deviants were lower in patients with TLE at the mastoid sites relative to controls, whereas the MMN amplitudes at the frontocentral sites did not differ between the two groups. There were no MMN differences related to frequency deviants between TLE subjects and controls at the frontocentral sites or the mastoid sites. Mismatch negativity parameters related to duration deviants did not correlate with those related to deviant frequencies in the group with TLE. The present findings suggest selective impairments among multiple mismatch generators in TLE and suggest that processing of temporal information of auditory stimuli is selectively disturbed in TLE. Changes in MMN amplitudes related to duration deviants at the mastoid sites may represent deficits in time-dependent processing in TLE.     

Finding the right control: The mismatch negativity under investigation

ObjectiveWhen investigating auditory perceptual regularity processing, mismatch negativity (MMN) is commonly used. MMN is computed as a difference signal between the event-related potentials (ERPs) elicited by repeated standard tones and rarely occurring deviant tones. This procedure leads to an underestimation of the N1 component elicited by standards compared to the N1 to deviants which might affect the MMN. Consequently, a random control design was previously introduced. This design, however, overestimates the N1 to the deviant. Here, we developed a new paradigm that avoids previous drawbacks.MethodsWe designed a regular cascadic sequence as a control to the deviant. ERPs were measured while presenting conventional oddball blocks (standards, deviants), random control blocks and a cascadic control block.ResultsMMN was observed in each difference signal. Regarding the N1, standards elicited smallest amplitudes. The N1 for the deviant and the cascadic control was comparable. The largest N1 was elicited by the random control.ConclusionStandards underestimate N1 refractoriness effects in the responses to deviants, while random control tones overestimate. Cascadic control tones, however, provide a reasonable estimation for the N1.SignificanceThe new cascadic control design is suitable to investigate auditory perceptual regularity processes while controlling for N1 refractoriness effects.     

Lasting first impressions: a conservative bias in automatic filters of the acoustic environment

Even in the unattended auditory environment, what we learn first appears resistant to re-evaluation based on experience. Mismatch negativity (MMN) is an auditory event-related potential elicited to rare deviation from automatically generated predictions about the sound environment. MMN amplitude is thought to reflect the potential importance of a sound for further processing. This study was designed to explore the degree to which past experience with a sound can alter automatic attributions about that sound's importance. MMN was elicited to rare (p = .125) physical “deviants” amongst a sequence of highly probable (p = .875) “standard” sounds. Sound identity alternated across blocks within the sequence (i.e., the former deviant became the new standard and the former standard the new deviant). The time period over which a standard remained the more probable tone was varied over Fast (0.8 min), Medium (1.6 min) and Slow (2.4 min) change conditions. Given that local within-block probabilities remained constant across conditions, any change in MMN size was considered a reflection of more rostral brain regions enabling a longer time scale (across-block) representation of event-probability extraction. Larger MMNs were expected to deviations in blocks with longer standard-stability. Although a significant increase in MMN amplitude was observed with increased rule stability, MMN amplitude was heavily dependent on the initial sequence structure. A “primacy bias” was observed such that prolonged stability produced large increases in the MMN to deviations from the first established standard but substantially smaller MMN to this first standard as a later deviant. The primacy effect in these data implies that the automatic filtering of sound relevance is biased toward a confirmation of initial expectations. Initial experience therefore altered the perceived salience of subsequent events.     

Right hemisphere dominance of different mismatch negativities

Auditory stimulus blocks were presented to 10 reading subjects. Each block consisted of 2 types of stimulus, standard (P = 90%) and deviant (P = 10%), delivered in a random order with short constant inter-stimulus intervals. The standard stimuli were 600 Hz, 80 dB SPL 50 msec sine wave bursts. In different blocks, the deviant stimuli differed from the standards either in frequency (650 Hz), intensity (70 dB) or duration (20 msec). Left- and right-ear stimulations were used in separate blocks. Event-related brain potentials (ERPs) were recorded with 16 electrodes over both hemispheres. All the different types of deviant stimuli elicited an ERP component called the mismatch negativity (MMN). The MMN was larger over the right hemisphere irrespective of the ear stimulated whereas the N1 component, elicited by both standards, and deviants, was larger over the hemisphere contralateral to the ear stimulated. The results provide further evidence for the view that the MMN reflects a neural mismatch process with a memory trace which automatically codes the physical features of the repetitive stimuli.     

Duration and frequency mismatch negativity in schizophrenia.

OBJECTIVES: The aim of the present study was to elucidate the reasons for apparent inconsistencies in the schizophrenia literature with respect to the mismatch negativity (MMN) waveform of the event-related potential (ERP). While most previous research has shown that MMN is reduced in schizophrenia, there are a small number of studies reporting that frequency MMN is not reduced. METHODS: We recorded ERPs to auditory stimuli with different frequencies and durations from patients with schizophrenia (N = 14) and control subjects (N = 17) of similar age and sex. MMNs to small but discriminable frequency deviants were contrasted with large frequency deviants and duration deviants. RESULTS: Only the MMN to duration deviants was significantly reduced in patients, although there was evidence of a similar trend for large frequency deviants. CONCLUSIONS: The results together with a review of the frequency MMN literature suggest that there are 3 variables which are important in determining whether patients exhibit a reduced MMN to frequency deviants: deviant probability, degree of deviance and interstimulus interval. The results also indicated that patients with schizophrenia may have particular deficits in processing the temporal properties of auditory stimuli. This finding has implications for the pathophysiology of the disorder as time-dependent processing is reliant on the integrity of an extensive network of brain areas consisting of auditory cortex, areas of pre-frontal cortex, the basal ganglia and cerebellum.     

Fast vigilance decrement in closed head injury patients as reflected by the mismatch negativity (MMN)

Event-related potentials (ERPs) were measured from 24 chronic closed head injury (CHI) patients and 18 age- and education-matched controls. The oddball paradigm was applied while subjects were watching a silent movie. The standard (p=0.8) sound of 75 ms duration had a basic frequency of 500 Hz with harmonic partials of 1000 Hz and 1500 Hz, whereas these frequencies for the pitch deviant were each 10% higher. The frequencies of the duration deviant matched with those of the standard but was 25 ms in duration. The MMN (mismatch negativity), generated by the brain's automatic auditory change-detector mechanism, was elicited by both deviants. No significant differences in the MMN latency or amplitude for either pitch or duration deviants were found between the groups. However, the MMN amplitude for the pitch deviant decreased in the patient group during the experiment considerably faster than in controls, suggesting a faster vigilance decrement in the patients.     

Do tone duration changes that elicit the mismatch negativity also affect the preceding middle latency responses?

The human brain can automatically detect sound changes. Previous studies have reported that rare sounds presented within a sequence of repetitive sounds elicit the mismatch negativity (MMN) in the absence of attention in the latency range of 100–250 ms. On the other hand, a previous study discovered that occasional changes in sound location enhance the middle latency response (MLR) elicited in the latency range of 10–50 ms. Several studies have reported an increase in the amplitude of the MLR within the frame of oddball paradigms such as frequency and location changes. However, few studies have been conducted on paradigms employing a duration change. The purpose of the present study was to examine whether the peak amplitudes of the MLR components are enhanced by a change in duration. Twenty healthy Japanese men (age: 23.9 ± 2.9 years) participated in the present study. We used an oddball paradigm that contained standard stimuli with a duration of 10 ms and deviant stimuli with a duration of 5 ms. The peak amplitudes of the MLR for the deviant stimuli were then compared with those for the standard stimuli. No changes were observed in the peak amplitude of the MLR resulting from a duration change, whereas a definite MMN was elicited. The amplitude of the MLR was increased within the frame of oddball paradigms such as frequency and location changes. By contrast, the amplitude of the MLR was not changed within the duration change oddball paradigm that elicited the MMN.     

Domain-specific suppression of auditory mismatch negativity with transcranial direct current stimulation

ObjectiveTo evaluate the influence of frontal transcranial direct current stimulation (tDCS) on auditory mismatch negativity (MMN).MethodsMMN is an event related potential calculated by subtracting the amplitude of the evoked potentials in response to a “standard” stimulus from the evoked potentials produced by a rare “oddball” stimulus. Here we assessed the influence of anodal tDCS, cathodal tDCS or sham stimulation delivered over the right inferior frontal cortex on MMN in response to duration and frequency auditory deviants in 10 healthy subjects.ResultsMMN to frequency deviants was significantly reduced after anodal tDCS compared with sham or cathodal stimulation which did not change MMN to frequency deviants. Neither anodal nor cathodal tDCS had any effect on MMN to duration deviants.ConclusionsNon-invasive brain stimulation with tDCS can influence MMN. The differing networks known to be activated by duration and frequency deviants could account for the differential effect of tDCS on duration and frequency MMN.SignificanceNon-invasive brain stimulation could be a useful method to manipulate MMN for experimental purposes.     

The effect of visual task difficulty and attentional direction on the detection of acoustic change as indexed by the Mismatch Negativity

Näätänen's model of auditory processing purports that attention does not affect the MMN. The present study investigates this claim through two different manipulations. First, the effect of visual task difficulty on the passively elicited MMN is assessed. Second, the MMNs elicited by stimuli under attended and ignored conditions are compared. In Experiment 1, subjects were presented with mixed sequences of equiprobable auditory and visual stimuli. The auditory stimuli consisted of standard (80 dB SPL 1000 Hz), frequency deviant (1050 Hz), and intensity deviant (70 dB SPL) tone pips. In a first instance, subjects were instructed to ignore the auditory stimulation and engage in an easy and difficult visual discrimination task (focused condition). Subsequently, they were asked to attend to both modalities and detect visual and auditory deviant stimuli (divided condition). The results indicate that the passively elicited MMN to frequency and intensity deviants did not significantly vary with visual task difficulty, in spite of the fact that the easy and difficult tasks showed a wide variation in performance. The manipulation of the attentional direction (focused vs. divided conditions) did result in a significant effect on the MMN elicited by the intensity, but not frequency, deviant. The intensity MMN was larger at frontal sites when subjects' attention was directed to both modalities as compared to only the visual modality. The attentional effect on the MMN to the intensity deviants only may be due to the specific deviant feature or the poorer perceptual discriminability of this deviant from the standard. Experiment 2 was designed to address this issue. The methods of Experiment 2 were identical to those of Experiment 1 with the exception that the intensity deviant (60 dB SPL) was made to be more perceptible than the frequency deviant (1016 Hz) when compared to the standard stimulus (80 dB SPL 1000 Hz). The results of Experiment 2 also demonstrated that the passively elicited MMN was not affected by large variations in visual task difficulty; this provides convincing evidence that the MMN is independent of visual task demands. Similarly to Experiment 1, the direction of attention again had a significant effect on the MMN. In Experiment 2, however, the frequency MMN (and not the intensity MMN) was larger at frontal sites during divided attention compared to focused visual attention. The most parsimonious explanation of these results is that attention enhances the discriminability of the deviant from the standard background stimulation. As such, small acoustic changes would benefit from attention whereas the discriminability of larger changes may not be significantly enhanced.     

Stability of the mismatch negativity under different stimulus and attention conditions.

OBJECTIVE: Mismatch negativities (MMN) elicited by frequency and duration changes in a sequence of repetitive tones were recorded in test and retest sessions from 45 subjects. METHODS: Tones presented with a stimulus onset asynchrony (SOA) of 0.5 s were to be ignored while attention had no instructed focus in one group and was directed to an active visual vigilance task in a second group of subjects. RESULTS: MMN amplitude was larger for duration deviants, the focus of attention had no systematic effect. Individual replicability of the MMN amplitudes was generally better when duration deviants were used. In addition, directing attention to the visual task increased the retest reliability of the duration deviance MMN. In this condition, the test-retest correlation coefficients were above 0.8 at all frontal scalp sites (0.87 at F4). CONCLUSIONS: The study shows that the deviant type as well as the attentional condition may have substantial effects on the stability and replicability of MMN potentials. The choice of the appropriate task condition is essential for using the MMN in group comparisons and as a diagnostic tool in individual cases.     

Informal musical activities are linked to auditory discrimination and attention in 2–3‐year‐old children: an event‐related potential study

The relation between informal musical activities at home and electrophysiological indices of neural auditory change detection was investigated in 2–3‐year‐old children. Auditory event‐related potentials were recorded in a multi‐feature paradigm that included frequency, duration, intensity, direction, gap deviants and attention‐catching novel sounds. Correlations were calculated between these responses and the amount of musical activity at home (i.e. musical play by the child and parental singing) reported by the parents. A higher overall amount of informal musical activity was associated with larger P3as elicited by the gap and duration deviants, and smaller late discriminative negativity responses elicited by all deviant types. Furthermore, more musical activities were linked to smaller P3as elicited by the novel sounds, whereas more paternal singing was associated with smaller reorienting negativity responses to these sounds. These results imply heightened sensitivity to temporal acoustic changes, more mature auditory change detection, and less distractibility in children with more informal musical activities in their home environment. Our results highlight the significance of informal musical experiences in enhancing the development of highly important auditory abilities in early childhood.     

The mismatch negativity during natural sleep: intensity deviants.

Auditory event-related potentials (ERPs) were recorded from 7 subjects who slept for a single night in the laboratory. An 'oddball' sequence of brief tone pips, differing in intensity, was used. Frequently occurring 70 dB 'standards' were presented with infrequent 80 dB intensity increment deviants and 60 dB intensity decrement deviants. The probability of each deviant was 0.1. Stimuli were presented in a random sequence every 600 ms while subjects were awake but inattentive and during stages 2 and REM of sleep. During wakefulness, the intensity increments elicited a broad fronto-central negativity with two discernable peaks. The first, peaking at approximately 120 ms, showed a polarity inversion at the mastoid and likely represented a summation of the N1 wave and the mismatch negativity (MMN). The second, peaking at approximately 330 ms, may have reflected an enhanced N2b component. In REM sleep, the increment deviants elicited a small amplitude 100-200 ms negativity but its amplitude was not significantly larger than the baseline level. It was followed by a larger and significant 300-450 ms negativity but this was considered too delayed to represent the MMN. The decrement deviants elicited a small amplitude, but statistically non-significant, MMN-like wave during both wakefulness and in REM sleep. A MMN-like wave was absent in stage 2 sleep.     

An electrophysiological and behavioral investigation of involuntary attention towards auditory frequency,duration and intensity changes

We measured behavior and event-related brain potentials (ERPs) in 12 subjects performing on an audio-visual distraction paradigm to investigate the cerebral mechanisms of involuntary attention towards stimulus changes in the acoustic environment. Subjects classified odd/even numbers presented on a computer screen 300 ms after the occurrence of a task-irrelevant auditory stimulus, by pressing the corresponding response button. Auditory stimuli were standard tones (600 Hz, 200 ms, 85 dB; P=0.8) or deviant tones (P=0.2), these differing from the standard either in frequency (700 Hz), duration (50 ms) or intensity (79 dB), in separate blocks. In comparison to performance to visual stimuli following the standard tones, reaction time increased by 24 ms (F(1,11)=10.91, P<0.01) and hit rate decreased by 4.6% (F(1,11)=35.47, P<0.001) to visual stimuli following the deviant tones, indicating behavioral distraction. ERPs revealed the mismatch negativity (MMN) elicited to deviant tones, which was larger for the duration deviant than for the frequency and intensity deviants (F(2,22)=19.43, P<0.001, epsilon =0.83), and which had different scalp distribution for all three deviant conditions (F(16,176)=2.40, P<0.05, epsilon =0.12). As the shorter duration and softer intensity deviant tones were unlikely to engage fresh neurons responding to their specific physical features, the present results indicate that a genuine change detection mechanism is involved in triggering attention switching towards sound changes, and suggest a largely distributed neural network of the auditory cortex underlying such involuntary attention switching.     

Mismatch negativity in schizophrenia: a meta-analysis

BACKGROUND: Mismatch negativity (MMN) is an auditory event-related potential that provides an index of automatic context-dependent information processing and auditory sensory memory. Many studies have reported abnormalities in the generation of MMN in schizophrenia. The objective of this study was to assess the magnitude of this deficit and associated factors. METHOD: Studies of MMN in schizophrenia were identified and included in a meta-analysis to estimate the mean effect size. Effects of duration of illness, gender ratio, age of patients, type of MMN (duration versus frequency MMN) and characteristics of the test paradigms (deviant probability, magnitude of standard-deviant difference) on effect size were assessed. RESULTS: Of 62 identified studies 32 met our inclusion criteria. The mean effect size was 0.99 (95% confidence intervals: 0.79, 1.29). Overall, no specific factor was significantly associated with MMN deficits, although MMN to stimuli differing in duration appeared more impaired in schizophrenia than MMN to frequency deviants. In addition, effect sizes of frequency MMN were significantly correlated with duration of illness. CONCLUSIONS: MMN deficits are a robust feature in chronic schizophrenia and indicate abnormalities in automatic context-dependent auditory information processing and auditory sensory memory in these patients. Reports of normal MMN in first-episode schizophrenia and the association of deficits in frequency MMN with illness duration suggest that MMN may index ongoing neuropathological changes in the auditory cortex in schizophrenia.     

Musical and linguistic expertise influence pre-attentive and attentive processing of non-speech sounds

The aim of this experiment was two-fold. Our first goal was to determine whether linguistic expertise influences the pre-attentive [as reflected by the Mismatch Negativity - (MMN)] and the attentive processing (as reflected by behavioural discrimination accuracy) of non-speech, harmonic sounds. The second was to directly compare the effects of linguistic and musical expertise. To this end, we compared non-musician native speakers of a quantity language, Finnish, in which duration is a phonemically contrastive cue, with French musicians and French non-musicians. Results revealed that pre-attentive and attentive processing of duration deviants was enhanced in Finn non-musicians and French musicians compared to French non-musicians. By contrast, MMN in French musicians was larger than in both Finns and French non-musicians for frequency deviants, whereas no between-group differences were found for intensity deviants. By showing similar effects of linguistic and musical expertise, these results argue in favor of common processing of duration in music and speech.     

Nicotine and the hallucinating brain: effects on mismatch negativity (MMN) in schizophrenia

Elevated smoking rates have been noted in schizophrenia, and it has been hypothetically attributed to nicotine's ameliorating abnormal brain processes in this illness. There is some preliminary evidence that nicotine may alter pre-attentive auditory change detection, as indexed by the EEG-derived mismatch negativity (MMN), but no previous study has examined what role auditory verbal hallucinations (AVH) may have on these effects. The objective of this study was to examine MMN-indexed acoustic change detection in schizophrenia (SZ) following nicotine administration and elucidate its association with AVH. Using a modified multi-feature paradigm, MMNs to duration, frequency and intensity deviants were recorded in 12 schizophrenia outpatients (SZ) with persistent AVHs following nicotine (6mg) and placebo administration. Electrical activity was recorded from 32 scalp electrodes; MMN amplitudes and latencies for each deviant were compared between treatments and were correlated with trait (PSYRATS) and state measures of AVH severity and Positive and Negative Syndrome Scale (PANSS) ratings. Nicotine administration resulted in a shortened latency for intensity MMN. Additionally, nicotine-related change in MMN amplitude was correlated with nicotine-related change in subjective measures of hallucinatory state. In summary, nicotine did not affect MMN amplitudes in schizophrenia patients with persistent AVHs, however this study reports accelerated auditory change detection to intensity deviants with nicotine in this group. Additionally, nicotine appeared to induce a generalized activation of the auditory cortex in schizophrenia, resulting in a concurrent increase in intensity MMN amplitude and subjective clarity of AVHs.     

Enhanced passive and active processing of syllables in musician children

The aim of this study was to examine the influence of musical expertise in 9-year-old children on passive (as reflected by MMN) and active (as reflected by discrimination accuracy) processing of speech sounds. Musician and nonmusician children were presented with a sequence of syllables that included standards and deviants in vowel frequency, vowel duration, and VOT. Both the passive and the active processing of duration and VOT deviants were enhanced in musician compared with nonmusician children. Moreover, although no effect was found on the passive processing of frequency, active frequency discrimination was enhanced in musician children. These findings are discussed in terms of common processing of acoustic features in music and speech and of positive transfer of training from music to the more abstract phonological representations of speech units (syllables).