Demonstration of mismatch negativity in the monkey

In humans, deviant auditory stimuli elicit an event-related potential (ERP) component, termed “mismatch negativity” (MMN), that reflects the operation of a cortical detector of infrequent stimulus change. Epidural auditory ERPs were recorded from 3 cynomolgous monkeys in response to soft and loud clicks. “Oddball” loud or soft stimuli elicited a long-duration frontocentral negativity, peaking at approximately 85 msec, that was superimposed upon cortically generated obligatory ERP components. These data suggest that monkeys might serve as a heuristically valuable system in which to study the neurochemical and neuroanatomical substrates of early context-dependent ERP generation.     

Why do we produce errors of commission? An ERP study of stimulus deviance detection and error monitoring in a choice go/no‐go task

The present study investigated event-related brain potential (ERP) reflections of stimulus deviance detection and error monitoring recorded during a go/no-go auditory oddball task. The mismatch negativity and error negativity were analysed as indices of these processes, respectively. We examined whether errors of commission occurred because of failures to detect stimulus deviance. On error trials the mismatch negativity amplitude did not differ between big and small deviant stimuli and was clearly reduced as compared with mismatch negativity amplitude on correct trials. Following an error response an error negativity was elicited, the amplitude of which was unaffected by stimulus deviancy. This pattern of ERP results was interpreted as supporting the defective deviance detection hypothesis.     

Event-related potentials in patients with obsessive-compulsive disorder

Twenty-three unmedicated patients with obsessive-compulsive disorder (OCD) were compared with 12 unmedicated patients with social phobia (SP) and 18 age-matched normal controls (C) using a two-tone auditory oddball event-related potentials (ERP) paradigm. The OCD group showed significantly shorter P300 latencies and shorter N200 latencies for target stimuli than the SP and the C groups. The OCD patients also tended to have greater N200 negativity compared with normal controls. However, there were no significant relationships between these ERP abnormalities in OCD patients and the type or severity of their OCD symptoms. In the mean ERP waveforms, increased N200 negativity for target stimuli, as well as the provocation in the later part of N200 for non-target stimuli, were more commonly observed in the OCD and the SP groups compared with the C group. These results raise the possibility that the shorter N200 and P300 latencies in OCD patients may be an OCD-specific phenomenon that is more closely related to the biological basis for OCD, rather than the characteristics of their OCD symptoms. On the other hand, increased negativity in the N200 region, even for non-target stimuli, may represent the common abnormalities among anxiety disorders.     

Early and late auditory event-related potentials in cognitively high functioning male adolescents with autism spectrum disorder

Event-related potentials (ERP) studies have offered diverging results in characterizing the basic nature of abnormal sensory processing and discrimination in autism spectrum disorders (ASDs). In the present study we report duration mismatch negativity (MMN) and later ERP components (P3a and P3b) derived from auditory odd-ball paradigms in a homogenous sample of cognitively high functioning male adolescents with ASD. We find significantly reduced frontal and temporal MMN amplitudes and no differences in P3a or P3b amplitudes or latencies compared to controls. These findings are in contrast to recent studies reporting enhanced ERP amplitudes to auditory stimuli, and are more in support of a weakened automatic auditory sensory processing as being central to the abnormal auditory behavioral responses commonly encountered in ASD.     

Event-related brain potential correlates of the processing of novel visual and auditory information in autism

Event-related brain potentials (ERPs) elicited by visual and auditory stimuli were recorded from nonretarded individuals with autism (ages 13-25 years) and age-matched normal controls. In "no-task" conditions, subjects simply looked at or listened to these stimuli; only one difference was found between subject groups. Several ERP differences between groups were found in "task" conditions; subjects pressed a button at the occurrence of target stimuli intermixed with unexpected, novel stimuli and also with expected, nonnovel stimuli. Visual ERP abnormalities in the autistic group differed from auditory abnormalities. Results suggest that (1) nonretarded autistic individuals may have a limited capacity to process novel information--they are neither hypersensitive to novel information nor misperceive it as nonnovel and insignificant; (2) classification of simple visual information may be less impaired than auditory; and (3) with one exception, visual and auditory ERP abnormalities do not seem to reflect maturational delay.     

Attending to visual or auditory motion affects perception within and across modalities: an event-related potential study

The present event-related potential (ERP) study examined the role of dynamic features in multisensory binding. It was tested whether endogenous attention to the direction of motion affects processing of visual and auditory stimuli within and across modalities. Human participants perceived horizontally moving dot patterns and sounds that were presented either continuously (standards) or briefly interrupted (infrequent deviants). Their task was to detect deviants moving in a particular direction within a primary modality, but to detect all deviants irrespective of their motion direction within the secondary modality. Attending to the direction of visual motion resulted in a broad selection negativity (SN) starting at about 200 ms post-stimulus onset, and attending to the direction of auditory motion resulted in a positive difference wave at 150 ms that was followed by a broad negativity starting at about 200 ms (unimodal effects). Moreover, dot patterns moving in a direction that was attended within audition were detected faster and more accurately than oppositely moving stimuli and elicited a cross-modal SN wave. Corresponding cross-modal behavioural and ERP results were obtained for sounds moving in a direction that was attended within vision. Unimodal and cross-modal ERP attention effects partially differed in their scalp topography. The present study shows that dynamic features (direction of motion) may be used to link input across modalities and demonstrates for the first time that these multisensory interactions take place as early as about 200 ms after stimulus onset.     

Mismatch negativity indexes auditory temporal resolution: evidence from event-related potential (ERP) and event-related field (ERF) recordings

This study examined auditory temporal resolution as indexed by gap detection using the mismatch negativity (MMN) component of the auditory event-related potential (ERP) and its magnetic counterpart (MMNm). ERPs were recorded in 10 subjects who were presented with auditory stimuli. These stimuli were presented in sequences of repetitive continuous 'standard' sinusoidal tones interspersed with infrequently occurring 'deviant' stimuli that differed from standards only in that they contained a silent gap midway in the stimulus. The gap size varied in separate stimulus blocks and was either 3, 5 or 7 ms. The stimuli were presented monaurally either to the left or the right ear. In a separate session, event-related magnetic fields (ERFs) were recorded from eight subjects using a similar paradigm but with gap sizes of 3, 7 or 11 ms and with binaural stimulation. Both ERP and ERF recordings showed that the smallest gap size (3 ms) did not elicit as large or reliable MMN or MMNm as did the larger ones. There were no differences in the laterality of the MMN as might be predicted on the basis of previous behavioural studies, but this result is likely a reflection of differences in task requirements. Nonetheless, the findings suggest that MMN and MMNm successfully index auditory temporal resolution thresholds, as measures that are independent of attention.     

Mismatch Negativity to Tonal Contours Suggests Preattentive Perception of Prosodic Content

Modulation of speech conveys information that is decoded within audio-sensory structures. For example, the termination of an utterance with a rise in pitch distinguishes statements and questions. This study evaluated the sensitivity of early auditory structures to such linguistic prosodic distinctions using mismatch negativity (MMN). MMN is a preattentive auditory event-related potential (ERP) sensitive to stimulus deviance. High-density ERP to pitch contour stimuli were collected in a passive listening oddball paradigm from 11 healthy subjects. Voltage analysis revealed significant MMN responses to declarative and interrogative oddball stimuli. Further, MMN was significantly larger to interrogative, than declarative, deviants, indicating non-symmetric brain processing. These MMNs demonstrate that pitch contour abstractions reflecting interrogative/ declarative distinctions can be represented in preattentive auditory sensory memory. This work was supported in part by NIMH grants NRSA F1-MH067339 (DIL), K02 MH01439 and R01 MH49334 (DCJ), R37 MH49334 and NS30029 (JJF), and a Translational Research Scientist Award from the Burroughs Welcome Fund (DCJ).     

On the possibility of independent activation of bilateral mismatch negativity (MMN) generators.

Event-related potential (ERP) studies on auditory selective attention have suggested that the neuronal traces underlying the mismatch negativity (MMN) develop separately for left and right ear inputs. We investigated whether this feature of the MMN could be exploited to activate the MMN generators in each hemisphere independently. Given the location of the MMN sources, this would allow separate assessment of left and right hemisphere auditory cortical structures. The MMN was elicited in a dichotic oddball paradigm using stimuli and conditions of stimulation that should optimize transmission of left and right ear stimuli to the contralateral auditory cortices. The MMN demonstrated no interhemispheric asymmetries, indicating that the bilateral MMN generators were symmetrically involved. The results of a supplementary experiment provide evidence for the simultaneous existence of multiple traces for MMN generation.     

Event-related brain potentials during auditory and visual word recognition memory tasks

Event-related brain potentials (ERPs) recorded during presentation of a series of words or pictures show enhanced positivity between 300 and 800 ms after presentation of repeated items. However, little attention has been directed to the characterization of this ERP recognition memory effect using auditory stimuli. The present study directly compared the ERP 'old/new effect' for words presented in the visual and auditory modalities. Nose-referenced ERPs were recorded from 30 electrode sites while participants (N=16) were engaged in visual and auditory continuous word recognition memory tasks. Spatially and temporally overlapping ERP components were identified and measured by covariance-based principal components analysis. The expected old/new effect was observed in both modalities, with a comparable time course peaking at 560 ms, but having a more anterior scalp topography for visual items. This suggests a common cognitive process (i.e. successful retrieval of information from memory) associated with separable neural generators in each modality. Despite this temporal synchronization, the old/new effect overlapped ERP components having distinct scalp topographies (N2) or peak latencies (P3) for each modality. The positive-going old/new effect was preceded by an earlier negativity peaking at 370 ms that was greater across modalities for old than new words, likely reflecting semantic processing aspects of word recognition memory. A late (beyond 900 ms), broadly-distributed negativity was also greater for old than new words, prolonged for auditory items, and may represent activity of a post-retrieval process.     

Selective attention and multisensory integration: multiple phases of effects on the evoked brain activity

We used event-related potentials (ERPs) to evaluate the role of attention in the integration of visual and auditory features of multisensory objects. This was done by contrasting the ERPs to multisensory stimuli (AV) to the sum of the ERPs to the corresponding auditory-only (A) and visual-only (V) stimuli [i.e., AV vs. (A + V)]. V, A, and VA stimuli were presented in random order to the left and right hemispaces. Subjects attended to a designated side to detect infrequent target stimuli in either modality there. The focus of this report is on the ERPs to the standard (i.e., nontarget) stimuli. We used rapid variable stimulus onset asynchronies (350-650 msec) to mitigate anticipatory activity and included "no-stim" trials to estimate and remove ERP overlap from residual anticipatory processes and from adjacent stimuli in the sequence. Spatial attention effects on the processing of the unisensory stimuli consisted of a modulation of visual P1 and N1 components (at 90-130 msec and 160-200 msec, respectively) and of the auditory N1 and processing negativity (100-200 msec). Attended versus unattended multisensory ERPs elicited a combination of these effects. Multisensory integration effects consisted of an initial frontal positivity around 100 msec that was larger for attended stimuli. This was followed by three phases of centro-medially distributed effects of integration and/or attention beginning at around 160 msec, and peaking at 190 (scalp positivity), 250 (negativity), and 300-500 msec (positivity) after stimulus onset. These integration effects were larger in amplitude for attended than for unattended stimuli, providing neural evidence that attention can modulate multisensory-integration processes at multiple stages.     

Abnormal mismatch negativity in women with sexual assault-related posttraumatic stress disorder.

BACKGROUND: Disturbances in sensory processing have been hypothesized in individuals with posttraumatic stress disorder (PTSD). The authors investigated this possibility by using mismatch negativity (MMN), an event-related potential (ERP) that reflects the operation of a preconscious cortical detector of stimulus change. METHODS: Thirteen medication-free women with sexual assault-related PTSD were compared with 16 age-matched, healthy comparison women without PTSD. ERPs were elicited by regularly presented "standard" auditory stimuli and by infrequently occurring "deviant" auditory stimuli, which differed slightly in frequency. The MMN was identified in the subtraction waveforms as the difference between ERPs elicited by the deviant and standard stimuli. Group comparisons of P50, N1, P2, and N2 to the standard and to the deviant stimuli, and of the MMN in the subtraction waveform were performed. RESULTS: The amplitude of the MMN was significantly greater in the PTSD compared to the non-PTSD women. MMN was significantly correlated with the total Mississippi PTSD Symptom Scale score in the PTSD group. No significant group differences were noted in P50, N1, or P2 responding. Significant group differences in N2 were due to the increased MMN in PTSD subjects. CONCLUSIONS: The data provide evidence for abnormalities in preconscious auditory sensory memory in PTSD, whereas earlier studies have reported abnormalities in conscious processing. These data suggest an increased sensitivity to stimulus changes in PTSD and implicate the auditory cortex in the pathophysiology of the disorder.     

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.     

Visual temporal window of integration as revealed by the visual mismatch negativity event-related potential to stimulus omissions

We studied whether, similarly to the auditory modality, short-period temporal integration processes occur in vision. Event-related potentials (ERP) were recorded for occasional stimulus omissions from sequences of patterned visual stimuli. A posterior negative component emerged only when the constant stimulus onset asynchrony (SOA) was shorter than 150 ms. This upper limit is comparable with the duration of the temporal window of integration observed in the auditory modality (including experiments studying the effects of stimulus omissions). Parameters of the posterior negativity were highly similar irrespective of whether the stimuli were task-relevant or not (Experiment 1). Thus, we identified this potential as the visual mismatch negativity (vMMN) component, which reflects task-independent detection of violating regularities of the stimulation. vMMN was followed by an anterior positivity (the P3a), indicating attentional shifts induced by the stimulus omissions. In Experiment 2, a posterior negativity similar to that observed in Experiment 1 emerged after the termination of short trains of stimuli, again only when the SOA was shorter than 150 ms. These results support the notion of a temporal integration window in the visual modality, the duration of which is between 150 and 180 ms.     

Cross-modal interactions between audition, touch, and vision in endogenous spatial attention: ERP evidence on preparatory states and sensory modulations

Recent behavioral and event-related brain potential (ERP) studies have revealed cross-modal interactions in endogenous spatial attention between vision and audition, plus vision and touch. The present ERP study investigated whether these interactions reflect supramodal attentional control mechanisms, and whether similar cross-modal interactions also exist between audition and touch. Participants directed attention to the side indicated by a cue to detect infrequent auditory or tactile targets at the cued side. The relevant modality (audition or touch) was blocked. Attentional control processes were reflected in systematic ERP modulations elicited during cued shifts of attention. An anterior negativity contralateral to the cued side was followed by a contralateral positivity at posterior sites. These effects were similar whether the cue signaled which side was relevant for audition or for touch. They also resembled previously observed ERP modulations for shifts of visual attention, thus implicating supramodal mechanisms in the control of spatial attention. Following each cue, single auditory, tactile, or visual stimuli were presented at the cued or uncued side. Although stimuli in task-irrelevant modalities could be completely ignored, visual and auditory ERPs were nevertheless affected by spatial attention when touch was relevant, revealing cross-modal interactions. When audition was relevant, visual ERPs, but not tactile ERPs, were affected by spatial attention, indicating that touch can be decoupled from cross-modal attention when task-irrelevant.     

Mismatch and conflict: neurophysiological and behavioral evidence for conflict priming

Conflict-related cognitive processes are critical for adapting to sudden environmental changes that confront the individual with inconsistent or ambiguous information. Thus, these processes play a crucial role to cope with daily life. Generally, conflicts tend to accumulate especially in complex and threatening situations. Therefore, the question arises how conflict-related cognitive processes are modulated by the close succession of conflicts. In the present study, we investigated the effect of interactions between different types of conflict on performance as well as on electrophysiological parameters. A task-irrelevant auditory stimulus and a task-relevant visual stimulus were presented successively. The auditory stimulus consisted of a standard or deviant tone, followed by a congruent or incongruent Stroop stimulus. After standard prestimuli, performance deteriorated for incongruent compared to congruent Stroop stimuli, which were accompanied by a widespread negativity for incongruent versus congruent stimuli in the event-related potentials (ERPs). However, after deviant prestimuli, performance was better for incongruent than for congruent Stroop stimuli and an additional early negativity in the ERP emerged with a fronto-central maximum. Our data show that deviant auditory prestimuli facilitate specifically the processing of stimulus-related conflict, providing evidence for a conflict-priming effect.     

Impaired temporal lobe processing of preattentive auditory discrimination in schizophrenia

Feature-specific stimulus discrimination related to short-term auditory sensory memory can be studied electrophysiologically using a specific event-related potential (ERP) component termed mismatch negativity (MMN), which is generated in the auditory cortex, indexing automatic comparison of the existing memory trace to incoming novel stimuli. Previous results with electroencephalography (EEG) and magnetoencephalography (MEG) suggest that schizophrenia patients have attenuated MMN response and that preattentive auditory processing preceding MMN appears to be functionally asymmetric in schizophrenia. Here we studied parallel MMN activity of the hemispheres using a whole-head MEG by presenting stimulus blocks consisting of frequent standard and infrequent deviant tones to 15 schizophrenia patients and 19 healthy control subjects. Auditory evoked fields (AEFs) were recorded simultaneously over both auditory cortices. The equivalent current dipole (ECD) modeling revealed that patients had significant MMNm reduction (magnetic counterpart of MMN) in both temporal lobes. In addition, patients had significantly delayed MMNm in the left but not in the right hemisphere to ipsilateral auditory stimuli. These results suggest that patients with schizophrenia have impaired auditory processing in the temporal lobes underlying preattentive stimulus discrimination that is also selectively delayed in the left hemisphere.     

A comparison of the mismatch negativity (MMN) event-related potential to tone and speech stimuli in normal and aphasic adults

Abstract

We evaluated the mismatch negativity (MMN) event-related potential (ERP) in normal and aphasic adults to tone and speech stimuli to determine aphasic patients' auditory discrimination and the relationship between MMN measures and severity of aphasia. MMNs were present in 89% of normal subjects and 79% of aphasic subjects to tone stimuli. MMNs were present in 100% of normal subjects and 54% of aphasic subjects to speech stimuli. The duration of the MMN ERP to speech stimuli was significantly related to severity of aphasia on the Western Aphasia Battery, Porch Index of Communicative Ability, and the Token Test. Thus, not all aphasic people show an early, preconscious orientation response to tone and speech stimuli. However, the duration of this response, when present, to speech stimuli appears to be related to the severity of aphasia.     

Potentials evoked in human and monkey medial temporal lobe during auditory and visual oddball paradigms.

Event-related potentials (ERPs) were recorded from epileptic patients with electrodes chronically implanted in the medial temporal lobe (MTL) and other intracranial locations, and from monkeys with epidural, transcortical, and MTL electrodes. For both humans and monkeys, the eliciting events consisted of trains of auditory or visual stimuli in which a random 10-20% deviated in pitch or pattern from the remaining stimuli. The distribution of ERPs elicited by the rare (oddball) stimuli in both species was similar, consisting of a P3 recorded from the scalp or cortical surface and a slightly later, but temporally overlapping, focal negativity in the hippocampus and nearby MTL structures. The similarity between the patterns of ERPs in humans and monkeys establishes the feasibility of studying the electrogenesis of P3-like activity with detailed intracranial recordings in an animal model. The data also establish that the MTL ERPs in human patients represent a normal neurophysiological process unrelated to epilepsy.     

P300 to high intensity stimuli during REM sleep.

OBJECTIVES: The P300 component of the auditory event-related potential (ERP) is a large amplitude positive wave peaking at approximately 300 ms following detection of a rare significant stimulus. Although P300 is typically only evoked when the subject attends to the stimulus, it may also be elicited in an awake, inattentive subject if the stimulus is sufficiently intrusive. We therefore employed an oddball task to determine if high intensity stimuli would elicit the P300 during sleep. METHODS: A loud 90 dB SPL tone pip was presented infrequently (P = 0.05) in a train of lower intensity 70 dB SPL standard stimuli. A multiple channel EEG was recorded from 8 good sleepers during a single night. RESULTS: A large amplitude parieto-central P300, peaking at 321 ms, was apparent in REM sleep to the loud deviant stimulus. In stage two non-REM sleep, a later positive wave, peaking at 446 ms, was apparent even after K-Complexes were removed from the average. This non-REM P450 was however maximum over occipito-parietal areas of the scalp. CONCLUSION: The presence of a P300 in REM sleep following a loud, rare stimulus indicates that sensory discrimination capabilities remain intact during this state. This may be associated with either pre- or conscious processing of relevant stimuli.