Measurement of extensive auditory discrimination profiles using the mismatch negativity (MMN) of the auditory event-related potential (ERP)

ObjectiveMismatch negativity (MMN), a change-specific component of the auditory event-related potential (ERP), is sensitive to deficits in central auditory processing associated with many clinical conditions. The aim of this study was to obtain a comprehensive multi-dimensional profile of central auditory processing by extending the recently developed fast multi-feature MMN paradigm [Näätänen R, Pakarinen S, Rinne T, Takegata R. The mismatch negativity (MMN): towards the optimal paradigm. Clin Neurophysiol 2004;115:140–144].MethodsMMN responses to changes in sound duration, frequency, intensity, and perceived sound-source location at six different magnitudes of deviation were recorded from healthy young adults by using the multi-feature MMN paradigm. In addition, behavioural discrimination accuracy and speed were measured to examine the relationship between MMN and behavioural performance.ResultsAll the 24 sound changes elicited significant MMNs. MMN amplitude increased and latency decreased with increasing magnitude of sound change. Furthermore, the MMN amplitude and latency predicted the subjects’ accuracy and speed in detecting these deviations.ConclusionsThis new paradigm provides an extensive auditory discrimination profile for several auditory attributes at different deviation magnitudes in a minimal recording time.SignificanceThe auditory discrimination profiles can offer a comprehensive view of the development, plasticity, and deficits of central auditory processing.     

An analysis of audio-visual crossmodal integration by means of event-related potential (ERP) recordings

Crossmodal integration was studied in humans by presenting random sequences of auditory (brief noise bursts), visual (flashes), and audiovisual (simultaneous noise bursts and flashes) stimuli from a central location at irregular intervals between 600 and 800 ms. The subjects' task was to press a button to infrequent and unpredictable (P=0.15) target stimuli that could be either a more intense noise burst, a brighter flash, or a combination of the two. In accordance with previous studies, behavioral data showed that bimodal target stimuli were responded to much faster and were identified more accurately than the unimodal target stimuli. The neural basis of this crossmodal interaction was investigated by subtracting the ERPs to the auditory (A) and the visual (V) stimuli alone from the ERP to the combined audiovisual (AV) stimuli (i.e. interaction=AV-(A+V)). Using this approach, we replicated previous reports of both early (at around 40 ms) and late (after 100 ms) ERP interaction effects. However, it appears that the very early interaction effects can be largely accounted for by an anticipatory ERP that precedes both the unimodal and bimodal stimuli. In calculating the ERP interaction this slow shift is subtracted twice, resulting in an apparent shift of the opposite polarity that may be confounded with actual crossmodal interactions.     

Mismatch negativity (MMN) in multiple sclerosis: an event-related potentials study in 46 patients.

OBJECTIVE: To assess pre-attentive detection mechanisms indexed by MMN component of auditory Event-Related Potentials (ERPs) in Multiple Sclerosis (MS) patients. METHODS: 46 MS patients (mean age 43.7 years, mean disease duration 10.1 years, mean EDSS 4.6) and 46 matched controls were assessed with ERPs elicited by a passive oddball paradigm using duration deviants. Auditory P50, N1, P2 components were recorded. MMN and P3a components were calculated as the difference potential between deviants and standard stimuli. Eighteen of these 46 patients underwent also global psychometrical assessment and were sorted in cognitively normal and impaired patients. ERPs of these two groups of patients were compared. RESULTS: MS patients showed reduced MMN and P3a areas as compared to controls, besides exogenous N1-P2 complex amplitude reduction. Among the 18 patients investigated with neuropsychological testings, six were cognitively impaired and 12 cognitively unimpaired. Patients with a global cognitive impairment had reduced MMN as compared to cognitively unimpaired patients. CONCLUSIONS: Auditory MMN and P3a components of auditory ERPs are altered in MS patients. MMN alterations are more pronounced in cognitively impaired patients. SIGNIFICANCE: MMN and P3a areas reduction suggests that MS patients are prone to pre-attentive auditory information processing deficits, besides previously described controlled information processing difficulties. Moreover, MMN alterations may represent an objective index of cognitive disturbances in MS patients.     

Cognition and aging: a highly selective overview of event-related potential (ERP) data

An overview of highly selected cognitive aging investigations of deviance detection, episodic memory and working memory reveals two primary themes: (1) when variability in elderly samples has been assessed, it has proven useful in understanding age-related changes in cognition; and (2) there is a frontal lobe contribution to at least some age-related changes in cognition. However, there are too few ERP age-related investigations of individual differences to determine whether the changes in patterns of ERP responding can be deemed "compensatory" or "inefficient." It is suggested that, to the extent possible, future electrophysiological investigations of cognitive aging (as well as other physiological measurement techniques) include individual difference measures that will enable the determination of the implication of a given neural pattern in the genesis of a given, age-related behavioral outcome pattern.     

Mismatch negativity (MMN) as a tool for investigating auditory discrimination and sensory memory in infants and children

For decades behavioral methods, such as the head-turning or sucking paradigms, have been the primary methods to investigate auditory discrimination, learning and the function of sensory memory in infancy and early childhood. During recent years, however, a new method for investigating these issues in children has emerged. This method makes use of the mismatch negativity (MMN), the brain's automatic change-detection response, which has been used intensively in both basic and clinical studies in adults for twenty years. This review demonstrates that, unlike many other components of event-related potentials, the MMN is developmentally quite stable and can be obtained even from pre-term infants. Further, MMN amplitude is only slightly smaller in infants than is usually reported in school-age children and it does not seem to differ much from that obtained in adults. MMN latency has been reported to be slightly longer in infants than in adults but reaches adult values by the early school-age years. Child MMN does not seem to be analogous to adult MMN, however. For example, contrary to the results of adult studies, a prominent MMN can be obtained from in all waking- and sleep states in infants. Moreover, MMN scalp distribution seems to be broader and more central in children than in adults.     

Age-related changes of auditory event-related potential (P300) in children

Auditory event-related potentials (ERPs) were recorded from 53 neurologically normal children of 5 to 15 years of age, and 8 healthy adults. To clarify the developmental changes and to obtain a normative value in childhood, the latency and amplitude of ERPs (N100, P200, N200, and P300) were examined. ERPs were elicited with the auditory oddball paradigm. P300 components were detected in all subjects. A strong positive correlation was demonstrated between latencies of two trials, and a small latency difference between trials was interpreted as being clinically unimportant. A significant negative correlation was observed between P300 latency and age during childhood (latency (msec) = -9.81 X (Age) + 459: r = 0.75, p less than 0.01). A mild negative correlation was also observed between N100, P200 and N200 latency and age. P300-topography of amplitude showed various patterns in young childhood, but in adolescence a maximum point was Pz in almost all subjects. These findings suggest that auditory ERPs can be easily measured in childhood and are useful for objective evaluation of the cognitive function.     

Sex differences in memory processing in schizophrenia: an event-related potential (ERP) study

Recently, research has begun to examine sex differences in cognitive functions in schizophrenia and whether such sex differences reflect normal, exaggerated, or reversed sexual dimorphism. This study examined this question by using event-related potentials (ERPs). ERPs were recorded in a recognition memory task in 18 patients and 18 matched control subjects. On an early frontal component, the results show an interaction between sex and pathological condition that results in an apparent reversed sexual dimorphism. On mid-latency components, patients show no sex difference on a frontal component, but a difference on the posterior component, whereas healthy subjects show a reverse pattern. Finally, late components show sex difference in the same direction as healthy subjects. These results indicate that the influence of sex on the cognitive impairment in schizophrenia is not homogenous across the information-processing cascade.     

Left temporal lobe dysfunction in schizophrenia: event-related potential and behavioral evidence from phonetic and tonal dichotic listening tasks

BACKGROUND: Asymmetric reduction of the P3 event-related potential (ERP) has provided evidence of left temporal lobe dysfunction in schizophrenia. Prior studies have been limited by reliance on simple target detection (oddball) tasks with pure tones. This study investigated the time course and topography of ERPs to binaural syllables or complex tones in dichotic listening tasks. METHODS: Event-related potentials of 26 patients meeting criteria for schizophrenia (n = 19) or schizoaffective disorder (n = 7) and 26 healthy controls were recorded from 30 scalp electrodes during 2 dichotic tasks in which different syllables or complex tones were simultaneously presented to each ear. A principal components analysis was used to derive factor scores corresponding to overlapping components in ERP waveforms--N1, N2, P3, and a late-positive potential. RESULTS: Healthy controls showed a right ear advantage for perceiving dichotic syllables, which was associated with greater N2 amplitude at left than right temporoparietal sites. Patients with schizophrenia did not show either this perceptual or N2 asymmetry. Patients also had smaller late-positive potential amplitude when compared with controls for both syllables and complex tones, with greatest decrement over left temporal sites. CONCLUSIONS: A right ear advantage in healthy adults for perceiving consonant-vowels was associated with a left-lateralized ERP component peaking at 200 milliseconds after syllable onset (N2). Patients with schizophrenia failed to show either of these task-dependent asymmetries, which may indicate a dysfunction of left temporal regions involved in phonetic classification. A task-independent asymmetric reduction of a later positive potential in patients with schizophrenia resembled left temporal P3 reductions reported for auditory oddball tasks.     

Event-related potential (ERP) evidence for fluency-based recognition memory

Two experiments investigated the influence of perceptual fluency on recognition memory. Words were studied using a shallow encoding task to decrease the contribution of recollection on recognition. Fluency was manipulated by blurring half of the test probes. Clarity varied randomly across trials in one experiment and was grouped into two blocks (clear and blurry) in the other experiment. Clarity did not influence recognition judgments or the ERP correlate of familiarity (FN400) when clarity was blocked across trials, but fluent probes (old and clear) elicited a more negative ERP than less fluent probes 280–400 ms at parietal electrode sites. Random variations in clarity produced the opposite pattern of results because recognition judgments and FN400 amplitudes varied, whereas the early ERPs did not differ. The results are interpreted as evidence that blocking clarity across trials led to recognition that was based on repetition fluency differences (i.e., old more fluent than new), which was associated with an early (280–400 ms) ERP at parietal electrodes in the absence of FN400 differences. Randomly varying clarity across trials created a situation where repetition fluency and perceptual fluency (i.e., probe clarity) interacted and led recognition to be based on familiarity/conceptual implicit memory that was associated with FN400 amplitudes in the absence of early ERP differences. The behavioral and ERP differences suggest that perceptual fluency, by itself, is capable of supporting recognition in some contexts and that, in other contexts, fluency can combine with other memory trace information to support recognition.     

Negative bias in expression-related mismatch negativity(MMN) in remitted late-life depression: An event-related potential study

Negative bias in cognition is closely associated with susceptibility to recurrent episodes of depression. Given the high recurrence rate of depression, previous studies have focused on the attentive level in late-life depression (LLD), but depression relapse is difficult to detect as a lower chief complaint in elderly people. Facial expression mismatch negativity (EMMN) is a tool that can measure cognitive bias in pre-attentive processing. In this study, we sought to explore the cognitive bias in pre-attentive emotional information processing in LLD. Thirty patients with remitted LLD and 30 non-depressed, age- and gender-matched normal controls (NC) were enrolled in this study. Automatic emotional processing was elicited by using an expression-related oddball paradigm in all participants. There were no significant differences in N170 amplitude and latency between remitted LLD and NC. Compared with NC subjects, patients with remitted LLD demonstrated an attenuated mean amplitude of positive and negative EMMN, whereas the mean amplitude of negative EMMN in remitted LLD was much larger than that of positive EMMN. Our findings suggest that although basic processing of facial expressions is intact in remitted LLD, automatic processing of facial expressions in remitted LLD is impaired with a negative bias in cognition. Further investigation of the contributions of negative bias in EMMN to susceptibility to recurrence of LLD is warranted.     

Absent event-related potential (ERP) word repetition effects in mild Alzheimer's disease.

OBJECTIVE: We hypothesized that an ERP word repetition paradigm, which reliably elicits and modulates the P600 and N400 components, would be particularly sensitive to the memory deficits and altered synaptic plasticity in mild Alzheimer's disease (AD). The P600 (a late positive component, or 'LPC'), and the N400, are sensitive indices of memory encoding and semantic processing, respectively. METHODS: We studied 11 patients with mild AD (mean MMSE=22.9) and 11 elderly (mean age=77.1) normal controls (NC) on a paradigm in which semantically 'congruous' category statement/exemplar pairs (50%) and 'incongruous' category statement/non-exemplar pairs (50%) repeat at 10-140 s intervals. A minimum of 19 channels ERP data were recorded and submitted to split-plot ANOVAs. RESULTS: Normal ERP data showed: (1) a significant word repetition effect for congruous words, with a wide-spread late positivity between approximately 300 and 800 ms post-stimulus (P600) that is larger for New than Old words; (2) a significant N400 repetition effect for incongruous words, with a right posterior negativity that is reduced for Old relative to New words. By contrast, neither of these word repetition effects was reliably present in the mild AD group. Good group discrimination was achieved by requiring that both these repetition effects were > or = the 10th percentile, with 100% sensitivity and 82% specificity. CONCLUSIONS: We found significant abnormalities of the N400 and P600 in mild AD, with both potentials showing markedly reduced sensitivity to word repetition. SIGNIFICANCE: The absence of normal N400 and LPC/P600 word repetition effects suggests impaired functioning of their neural generators, several of which are located in medial temporal lobe predilection sites (e.g. anterior fusiform, parahippocampal gyrus, hippocampus) for AD/tau pathology.     

Evaluation of reading comprehension with neuropsychological and event-related brain potential (ERP) methods.

Evidence is presented for the efficacy of a new method of assessing reading comprehension using a standardized reading test that was formatted for computer presentation with simultaneous event-related brain potential (ERP) recordings. Reading comprehension abilities of 23 healthy undergraduate students were evaluated using ERPs. The results revealed a differential ERP response pattern for correct and incorrect test items. These response patterns were observed at individual participant levels. The findings provided further support for the use of ERPs in the neuropsychological assessment of patients who are difficult or impossible to assess using behavioral responses because of concomitant motoric and/or communicative limitations.     

Local and global auditory processing: behavioral and ERP evidence

Differential processing of local and global visual features is well established. Global precedence effects, differences in event-related potentials (ERPs) elicited when attention is focused on local versus global levels, and hemispheric specialization for local and global features all indicate that relative scale of detail is an important distinction in visual processing. Observing analogous differential processing of local and global auditory information would suggest that scale of detail is a general organizational principle of the brain. However, to date the research on auditory local and global processing has primarily focused on music perception or on the perceptual analysis of relatively higher and lower frequencies. The study described here suggests that temporal aspects of auditory stimuli better capture the local-global distinction. By combining short (40 ms) frequency modulated tones in series to create global auditory patterns (500 ms), we independently varied whether pitch increased or decreased over short time spans (local) and longer time spans (global). Accuracy and reaction time measures revealed better performance for global judgments and asymmetric interference that were modulated by amount of pitch change. ERPs recorded while participants listened to identical sounds and indicated the direction of pitch change at the local or global levels provided evidence for differential processing similar to that found in ERP studies employing hierarchical visual stimuli. ERP measures failed to provide evidence for lateralization of local and global auditory perception, but differences in distributions suggest preferential processing in more ventral and dorsal areas respectively.     

Discerning temporal expectancy effects in script processing: evidence from pupillary and eye movement recordings

Accessing the temporal position of events (early or late in the event sequence) can influence the generation of predictions about upcoming events. However, it is unclear how the temporal position is processed strategically. To investigate this, we presented event pairs to 23 healthy volunteers manipulating temporal order (chronological, inverse) and temporal position (early, late). Pupil dilation, eye movements, and behavioral data, showed that chronological and early event pairs are processed with more ease than inverse and late event pairs. Indexed by the pupillary response late events and inversely presented event pairs elicited greater cognitive processing demands than early events and chronologically presented event pairs. Regarding eye movements, fixation duration was less sensitive to temporal position than to temporal order. Looking at each item of the event sequence only once was behaviorally more effective than looking multiple times at each event regardless of whether temporal position or temporal order was processed. These results emphasize that accessing temporal position and temporal order information results in dissociable behavioral patterns. While more cognitive resources are necessary for processing late and inverse items, change of information acquisition strategies turns out to be most effective when temporal order processing is required.     

Spatial location is accurately tracked by human auditory sensory memory: evidence from the mismatch negativity

The nature of spatial representation in human auditory cortex remains elusive. In particular, although humans can discriminate the locations of sounds as close as 1-10 degrees apart, such resolution has not been shown in auditory cortex of humans or animals. We used the mismatch negativity (MMN) event related brain potential to measure the neural response to spatial change in humans in narrow 10 degree spatial steps. Twelve participants were tested using a dense array EEG setup while watching a silent movie and ignoring the sounds. The MMN was reliably elicited by infrequent changes of spatial location of sounds in free field. The MMN amplitude was linearly related to the degree of spatial change with a resolution of at least 10 degrees. These electrophysiological responses occurred within a window of 100-200 milliseconds from stimulus onset, and were localized to the posterior superior temporal gyrus. We conclude that azimuthal spatial displacement is rapidly, accurately and automatically represented in auditory sensory memory in humans, at the level of the auditory cortex.     

Fine grain temporal analysis in aphasia: evidence from auditory gap detection

Auditory temporal processing was investigated in individuals with acquired aphasia using a task in which they were asked to detect brief silent gaps inserted between noise segments modeled after formants in speech. To examine within-channel gap detection, gaps of 10, 20, 40, and 80ms duration were inserted between an initial segment (IS) and a trailing segment (TS) centered at the same frequency (1kHz). In a between-channel gap detection condition, gaps of 20, 40, 80, and 100ms duration were inserted between an IS that differed in frequency (4kHz) from the TS (1kHz). The effect of gap onset timing was examined in both conditions by systematically varying the duration of the IS by 10, 20, or 40ms. A combined analysis revealed that for both conditions and all gap and IS durations, individuals with aphasia produced fewer correct responses than age-matched neurologically intact controls. Separate condition analyses revealed that when noise segments were centered at the same frequency, individuals with aphasia demonstrated poorer accuracy in detecting 40 and 80ms gaps relative to normal controls (p<0.001). When gaps were inserted between noise segments differing in frequency, on average, aphasic subjects performed less accurately at durations of 40, 80 and 100ms (p<0.025). Detection in both groups decreased with smaller IS durations. The difficulties with gap detection observed in the aphasic group suggest the existence of fundamental problems in processing the temporal form or microstructure of sounds characterized by rapidly changing onset dynamics.     

Effects of simulated high altitude on event-related potential (P300) and auditory brain-stem responses.

OBJECTIVE: This study investigated the effect of hyobaric hypoxia on cognitive function. METHODS: We recorded the auditory brain-stem response (ABR) and auditory-evoked event-related potentials (ERP) in 7 male subjects during a rapid ascent to a simulated 4500 m altitude from their acclimatized altitude of 610 m. The amplitude and latency of each component of ABR and of ERP were assessed. RESULTS: Compared with the values at 610 m, at 4500 m the latencies of both waves I and V of ABR significantly increased, with no change in I-V interpeak latency; and the amplitude of wave I decreased, with no change in the amplitude of wave V. The increase in altitude affected neither the amplitude nor the latency of N100. The P300 latency was prolonged significantly after exposure to hypobaric-hypoxic conditions for 2h, with no significant change in amplitude. At 4500 m, the P300 latency returned to the baseline value after oxygen was inhaled. CONCLUSIONS: Our results suggest it is possible to boost cognitive processing by supplying oxygen even when auditory stimulus intensity decreases under hypobaric and hypoxic conditions, and that P300 latency is affected by hypoxic more than hypobaric conditions. SIGNIFICANCE: This study demonstrated that each component of ABR and the latency of both N100 and P300 are important to record when the effects of hypobaric hypoxia on cognitive function are investigated.     

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.     

The novelty P3: an event-related brain potential (ERP) sign of the brain's evaluation of novelty.

A review of the literature that examines event-related brain potentials (ERPs) and novelty processing reveals that the orienting response engendered by deviant or unexpected events consists of a characteristic ERP pattern, comprised sequentially of the mismatch negativity (MMN) and the novelty P3 or P3a. A wide variety of evidence suggests that the MMN reflects the detection of deviant events, whereas the P3a is associated more with the evaluation of those events for subsequent behavioral action. On the scalp, the novelty P3a is comprised of at least two aspects, one frontal the other posterior, each with different cognitive (and presumably neurologic) correlates. Intracranial ERP investigations and studies of patients with localized brain lesions (and, to some extent, fMRI data) converge with the scalp-recorded data in suggesting a widespread neural network, the different aspects of which respond differentially to stimulus and task characteristics.     

Mismatch negativity (MMN) stands at the crossroads between explicit and implicit emotional processing

The amygdala is known as a key brain region involved in the explicit and implicit processing of emotional faces, and plays a crucial role in salience detection. Not until recently was the mismatch negativity (MMN), a component of the event‐related potentials to an odd stimulus in a sequence of stimuli, utilized as an index of preattentive salience detection of emotional voice processing. However, their relationship remains to be delineated. This study combined the fMRI scanning and event‐related potential recording by examining amygdala reactivity in response to explicit and implicit (backward masked) perception of fearful and angry faces, along with recording MMN in response to the fearfully and angrily spoken syllables dada in healthy subjects who varied in trait anxiety (STAI‐T). Results indicated that the amplitudes of fearful MMN were positively correlated with left amygdala reactivity to explicit perception of fear, but negatively correlated with right amygdala reactivity to implicit perception of fear. The fearful MMN predicted STAI‐T along with left amygdala reactivity to explicit fear, whereas the association between fearful MMN and STAI‐T was mediated by right amygdala reactivity to implicit fear. These findings suggest that amygdala reactivity in response to explicit and implicit threatening faces exhibits opposite associations with emotional MMN. In terms of emotional processing, MMN not only reflects preattentive saliency detection but also stands at the crossroads of explicit and implicit perception. Hum Brain Mapp 38:140–150, 2017. © 2016 Wiley Periodicals, Inc.