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In this article, we review clinical research using the mismatch negativity (MMN), a change-detection response of the brain elicited even in the absence of attention or behavioural task. In these studies, the MMN was usually elicited by employing occasional frequency, duration or speech-sound changes in repetitive background stimulation while the patient was reading or watching videos. It was found that in a large number of different neuropsychiatric, neurological and neurodevelopmental disorders, as well as in normal ageing, the MMN amplitude was attenuated and peak latency prolonged. Besides indexing decreased discrimination accuracy, these effects may also reflect, depending on the specific stimulus paradigm used, decreased sensory-memory duration, abnormal perception or attention control or, most importantly, cognitive decline. In fact, MMN deficiency appears to index cognitive decline irrespective of the specific symptomatologies and aetiologies of the different disorders involved.

Cognitive impairment is a core element shared by a large number of different neurological and neuropsychiatric diseases. Irrespective of their different aetiologies and symptomatologies, most appear to converge at the functional deficiency of the auditory-frontal cortex network of auditory discrimination, which indexes cognitive impairment shared by these abnormalities. This auditory-frontal cortical deficiency, and hence cognitive decline, can now be objectively measured with the mismatch negativity and its magnetic equivalent. The auditory-frontal cortical network involved seems, therefore, to play a pivotal, unifying role in the different abnormalities. It is, however, more likely that the dysfunction that can be detected with the mismatch negativity and its magnetoencephalographic equivalent manifests a more widespread brain disorder, namely, a deficient N -methyl-d-aspartate receptor function, shared by these abnormalities and accounting for most of the cognitive decline. * Abbreviation : MMN : mismatch negativity

Background: The mismatch negativity (MMN) is a fronto-centrally distributed event-related potential (ERP) that is elicited by any discriminable auditory change. It is an ideal neurophysiological tool for measuring the auditory processing skills of individuals with aphasia because it can be elicited even in the absence of attention. Previous MMN studies have shown that acoustic processing of tone or pitch deviance is relatively preserved in aphasia, whereas the basic acoustic processing of speech stimuli can be impaired (e.g., auditory discrimination). However, no MMN study has yet investigated the higher levels of auditory processing, such as language-specific phonological and/or lexical processing, in individuals with aphasia. Aims: The aim of the current study was to investigate the MMN responses of normal and language-disordered subjects to tone stimuli and speech stimuli that incorporate the basic auditory processing (acoustic, acoustic-phonetic) levels of non-speech and speech sound processing, and a...

The purpose of this study was to determine whether the presence of subtitles on a distracting, silent video affects the automatic mismatch negativity (MMN) response to simple tones, consonant-vowel (CV) nonwords, or CV words. Two experiments were conducted in this study, each including ten healthy young adult subjects. Experiment 1 investigated the effects of subtitles on the MMN response to simple tones (differing in frequency, duration, and intensity) and speech stimuli (CV nonwords and CV words with a /d/-/g/ contrast). Experiment 2 investigated the effects of subtitles on the MMN response to a variety of CV nonword and word contrasts that incorporated both small (e.g., /d/ vs. /g/) and/or large (e.g., /e:/ vs. /el/) acoustic deviances.The results indicated that the presence or absence of subtitles on the distracting silent video had no effect on the amplitude of the MMN or P3a responses to simple tones, CV nonwords, or CV words. In addition, the results also indicated that movement artifacts may be statistically reduced by the presence of subtitles on a distracting silent video. The implications of these results are that more "engaging" (i.e., subtitled) silent videos can be used as a distraction task for investigations into MMN responses to speech and nonspeech stimuli in young adult subjects, without affecting the amplitude of the responses.

Human auditory system maturation as assessed by means of auditory-evoked potential recording is compared to maturation of axon neurofilaments and some critical stages in speech perception. The parallels strongly suggest that the emergence of the N1 component reflects the maturation of the axons in layer II and upper layer III of the auditory cortex. This is also the time period during which the perception of speech in noise and degraded speech markedly improves. The absence of N1 in cochlear implant subjects who have been deaf for a period of at least 3 years below the age of 6 years suggests a critical period in the maturation of the upper cortical layers and potentially poor future performance in the perception of masked and degraded speech.

Evoked electric potential and magnetic field studies have the immense benefit that they can be conducted in awake, behaving humans and can be directly correlated with aspects of perception. As such, they are powerful objective indicators of perceptual properties. However, given a set of evoked potential and/or evoked field waveforms and their source locations, obtained for an exhaustive set of stimuli and stimulus contrasts, is it possible to determine blindly, i.e. predict, what the stimuli or stimulus contrasts were? If this can be done with some success, then a useful amount of information resides in scalp-recorded activity for, e.g., the study of auditory speech processing. In this review, we compare neural representations based on single-unit and evoked response activity for vowels and consonant-vowel phonemes with distinctions in formant glides and voice onset time. We conclude that temporal aspects of evoked responses can track some of the dominant response features present in single-unit activity. However, N1 morphology does not reliably predict phonetic identification of stimuli varying in voice onset time, and the reported appearance of a double-peak onset response in aggregate recordings from the auditory cortex does not indicate a cortical correlate of the perception of voicelessness. This suggests that temporal aspects of single-unit population activity are likely not inclusive enough for representation of categorical perception boundaries. In contrast to population activity based on single-unit recording, the ability to accurately localize the sources of scalp-evoked activity is one of the bottlenecks in obtaining an accessible neurophysiological substrate of perception. Attaining this is one of the requisites to arrive at the prospect of blind determination of stimuli on the basis of evoked responses. At the current sophistication level of recording and analysis, evoked responses remain in the realm of extremely sensitive objective indicators of stimulus change or stimulus differences. As such, they are signs of perceptual activity, but not comprehensive representations thereof.

Experience-related changes in central nervous system (CNS) activity have been observed in the adult brain of many mammalian species, including humans. In humans, late-onset profound unilateral deafness creates an opportunity to study plasticity in the adult CNS consequent to monaural auditory deprivation. CNS activity was assessed by measuring long-latency auditory evoked potentials (AEPs) recorded from teens and adults with late-onset (post-childhood) profound unilateral deafness. Compared to monaurally stimulated normal-hearing subjects, the AEPs recorded from central electrode sites located over auditory cortical areas showed significant increases in inter-hemispheric waveform cross-correlation coefficients, and in inter-hemispheric AEP peak amplitude correlations. These increases provide evidence of substantial changes from the normal pattern of asymmetrical (contralateral > ipsilateral amplitude) and asynchronous (contralateral earlier than ipsilateral) central auditory system activation in the normal-hearing population to a much more symmetrical and synchronous activation in the unilaterally deaf. These cross-sectional analyses of AEP data recorded from the unilaterally deaf also suggest that the changes in cortical activity occur gradually and continue for at least 2 years after the onset of hearing loss. Analyses of peak amplitude correlations suggest that the increased inter-hemispheric symmetry may be a consequence of changes in the generators producing the N (approximately 100 ms peak latency) potential. These experience-related changes in central auditory system activity following late-onset profound unilateral deafness thus provide evidence of the presence and the time course of auditory system plasticity in the adult brain.

To determine whether the N1-P2 complex reflects training-induced changes in neural activity associated with improved voice-onset-time (VOT) perception.Auditory cortical evoked potentials N1 and P2 were obtained from 10 normal-hearing young adults in response to two synthetic speech variants of the syllable /ba/. Using a repeated measures design, subjects were tested before and after training both behaviorally and neurophysiologically to determine whether there were training-related changes. In between pre- and post-testing sessions, subjects were trained to distinguish the -20 and -10 msec VOT /ba/ syllables as being different from each other. Two stimulus presentation rates were used during electrophysiologic testing (390 msec and 910 msec interstimulus interval).Before training, subjects perceived both the -20 msec and -10 msec VOT stimuli as /ba/. Through training, subjects learned to identify the -20 msec VOT stimulus as "mba" and -10 msec VOT stimulus as "ba." As subjects learned to correctly identify the difference between the -20 msec and -10 msec VOT syllabi, an increase in N1-P2 peak-to-peak amplitude was observed. The effects of training were most obvious at the slower stimulus presentation rate.As perception improved, N1-P2 amplitude increased. These changes in waveform morphology are thought to reflect increases in neural synchrony as well as strengthened neural connections associated with improved speech perception. These findings suggest that the N1-P2 complex may have clinical applications as an objective physiologic correlate of speech-sound representation associated with speech-sound training.

The use of cochlear implants to restore auditory sensation in deaf children is increasing, with a trend toward earlier implantation. However, little is known about how auditory deprivation and subsequent cochlear implant use affect the maturing human central auditory system. Our previous studies have demonstrated that the obligatory auditory evoked potentials (AEPs) of implanted children are very different from those of normal-hearing children. Unlike the obligatory potentials, which primarily reflect neural responses to stimulus onset, the mismatch negativity (MMN) provides a neurophysiological measure of auditory short-term memory and discrimination processes. The purpose of this investigation is to review our studies of the effects of auditory deprivation due to profound deafness and cochlear implant use on the maturation of the MMN in children, placed in the context of overall age-related changes in the AEPs. The development and application of a statistical technique to assess the MMN in individuals is also reviewed. Results show that although the morphology of the obligatory AEPs is substantially altered by the absence of a normal N1 peak, the MMN is robustly present in a group of implanted children who have good spoken language perception through their device. Differences exist in the scalp distribution of the MMN between implanted and normal-hearing children. Specifically, the MMN appears to be more symmetrical in amplitude over both hemispheres, whereas it is initially much larger over the contralateral hemisphere in normal-hearing children. These findings suggest that, compared to N1, the MMN is a better measure of basic auditory processes necessary for the development of spoken language perception skills in profoundly deaf children and adults who use a cochlear implant.

Derived-band auditory brainstem responses (ABRs) were obtained in 43 normal-hearing and 80 cochlear hearing-impaired individuals using clicks and high-pass noise masking. The response times across the cochlea [the latency difference between wave V's of the 5.7- and 1.4-kHz center frequency (CF) derived bands] were calculated for five levels of click stimulation ranging from 53 to 93 dB p.-p.e. SPL (23 to 63 dB nHL) in 10-dB steps. Cochlear response times appeared to shorten significantly with hearing loss, especially when the average pure tone (1 to 8 kHz) hearing loss exceeded 30 dB. Examination of derived-band latencies indicates that this shortening is due to a dramatic decrease of wave V latency in the lower CF derived band. Estimates of cochlear filter times in terms of the number of periods to maximum response (Nmax) were calculated from derived-band latencies corrected for gender-dependent cochlear transport and neural conduction times. Nmax decreased as a function of hearing loss, especially for the low CF derived bands. The functions were similar for both males and females. These results are consistent with broader cochlear tuning due to peripheral hearing loss. Estimating filter response times from ABR latencies enhances objective noninvasive diagnosis and allows delineation of the differential effects of pathology on the underlying cochlear mechanisms involved in cochlear transport and filter build-up times.

The auditory brain‐stem responses (ABRs) to rarefaction and condensation clicks were obtained for 12 normal‐hearing subjects in quiet, and high‐pass masking at 8, 4, 2, 1, and 0.5 kHz. Derived narrow‐band wave V latency differences were analyzed with respect to (1) stimulus polarity, (2) absolute differences irrespective of polarity. The analyses revealed no significant stimulus polarity effects on latency for the derived bands. Absolute latency differences regardless of polarity tended to be greater for those derived bands having lower characteristic frequencies (CFs). However, these differences were smaller than the expected half‐period of the theoretical CF. Further analyses in three additional subjects using repeated runs of the same polarity indicate that this increase in absolute latency difference with lower derived band CF does not reflect a simple half‐period change owing to polarity, but rather to the increase variability in measuring the peak latency of the lower CF derived bands. The variability is consistent with variability of eighth nerve PST histograms behavior observed in animal work [Kiang et al., ‘‘Discharge patterns of single fibers in the cat’s auditory nerve,’’ Research Monograph No. 35 (MIT, Cambridge, MA, 1965)]. Thus claimed polarity effects observed in other ABR work using absolute values may have been affected by this variability. It appears from these current data that half‐period latency shifts of wave V owing to stimulus polarity differences are not observed in derived bands responses initiated from frequency specific regions of the cochlea.

Previously, it was shown [Don et al., J. Acoust. Soc. Am. 94, 2135-2148 (1993)] that cochlear response times are gender specific and about 13% shorter in females than in males. It is also suggested that one of the possible reasons click-evoked auditory brainstem response (ABR) waveforms recorded from females are better defined and have larger amplitudes than those of males is due to a sex difference in cochlear response times leading to better synchronization of the cochlear output across the frequency regions. Variability in cochlear response times would also lead to variability in click evoked ABR amplitudes. The high-pass noise masking derived ABR technique was used to investigate the effect of normalizing the individual temporal variability at the neural and cochlear levels. This involved adjusting for differences in neural conduction time (I-V delay) by a compression or expansion of the derived ABR waveforms and by adjusting for differences in cochlear response times by a shift of the derived ABR waveforms. A summation of the compressed and shifted ABRs results in a normalized unmasked ABR waveform that can then be compared for amplitude variability with the unprocessed unmasked ABRs. Compensation for the neutral I-V variability had little effect while compensation for cochlear response times, particularly the delay between the 5.7- and 2.8-kHz regions, greatly affected the amplitude of wave V of the compounded ABR. This work provides a better understanding of the significant relationship between cochlear response times and variability of the ABR peak amplitudes.

Derived narrow-band auditory brain-stem responses (ABRs) in young normal-hearing subjects revealed a significant gender difference in response time between frequency regions of the cochlea. Females showed shorter delays than males between derived bands. This differential has not been previously reported. As in many early studies, the unmasked amplitude of the wave V complex was significantly larger (30%) in females than males. However, differences in amplitudes of the narrow-band responses were too small to account for the differential in the unmasked response. It is hypothesized that the larger amplitude of the unmasked wave V complex in females occurs because of a faster response time across the cochlea leading to better neural synchrony and, therefore, larger amplitudes. Furthermore, results can be explained by assuming that the stiffness gradient in the cochlea is 13% larger in females than in males. If males and females have the same cochlear tonotopic mapping, the female cochlea should be 13% shorter. This prediction is highly consistent with recent anatomical studies of cochlear length and gender. The results of the present study indicated possibly important cochlear mechanisms that influence the main parameters of ABRs. An understanding of these cochlear mechanisms may improve the diagnostic capabilities of ABRs in patients with peripheral hearing loss.

The high-pass noise masking technique was used to obtain derived frequency-specific cochlear microphonics (CM) from subtracted waveforms to rarefaction and condensation stimuli recorded with a tympanic membrane electrode. Two characteristics suggest that the response is place-specific CM: the derived response retains the same frequency as the stimulating toneburst and the response follows the stimulus polarity. For click stimulation, derived neural responses make the place-specific CM difficult to observe except in the 2-1 kHz derived band. In contrast, place-specific CM evoked by 0.5 and 1 kHz tonebursts can usually be detected in at least three derived bands. The amplitude of the response is largest in the derived band with center-frequency (CF) just above that of the toneburst. This discovery of a place-specific CM offers the possibility of assessing (outer) hair cell function in the apical part of the human cochlea.

Ototoxicity is an adverse side effect of numerous therapeutic agents (amino-glycoside antibiotics, blood chelating agents, diuretics and oncologic drugs) used in treatment of both adult and pediatric patients. Recently, there has been increasing interest in using the auditory brainstem response (ABR) to detect both short-term effects of ototoxicity in adults and long-term effects of drug administration on neonates and children. Since click ABRs have relatively poor frequency selectivity they best approximate the pure-tone hearing threshold in the 2000-4000 Hz frequency range. Hearing loss above or below that frequency range can be present without producing significant abnormalities in the ABR waveform parameters. Frequency-specific ABRs can be obtained using the derived response technique. The purpose of this study was to investigate early cisplatin ototoxicity using both the broadband click and derived ABR and to monitor progressive hearing loss with repeated drug trials in 18 patients studied over a 2-year period. ABRs were obtained serially prior to and following intravenous administration of cisplatin. Derived ABRs were found to be more sensitive than broadband click ABR in detecting early high-frequency hearing loss. For click ABRs, the cumulative dosage of cisplatin at age of ABR examination was correlated with hearing loss in only those patients under 3 years of age. No significant correlation was found between cumulative cisplatin dosage when tested and degree of hearing loss in those patients over 3 years of age.

This chapter describes the effects that a period of auditory deprivation due to profound deafness, followed by restoration of sensation via a cochlear implant, has on the development of the human auditory central nervous system. Neurophysiological evidence of human central auditory system plasticity in profoundly deaf adults and children who use cochlear prostheses will be based on scalp-recorded electrophysiological activity evoked by activation of the cochlear implant. This activity measured from cochlear implant users is contrasted with that of normal-hearing adults and children to illustrate the similarities and differences in auditory cortical activity. These results are set in the context of what is known about the generators of the AEPs (auditory evoked potentials) as well as recent studies describing the maturational sequence of the neuroanatomical structures, particularly in cortex.

Objective The aim was to determine whether children with specific language impairment (SLI) differed from children with typical language development (TLD) in their allocation of attention to speech sounds. Methods Event-related potentials were recorded to non-target speech sounds in two tasks (passive-watch a video and attend to target tones among speech sounds) in two experiments, one using 50-ms duration vowels and the second using 250-ms vowels. The difference in ERPs across tasks was examined in the latency range of the early negative difference wave (Nd) found in adults. Analyses of the data using selected superior and inferior sites were compared to those using electrical field power (i.e., global field power or GFP). The topography of the ERP at the maximum GFP was also examined. Results A negative difference, comparable to the adult Nd, was observed in the attend compared to the passive task for both types of analysis, suggesting allocation of attentional resources to processing the speech stimuli in the attend task. Children with TLD also showed greater negativity than those with SLI in the passive task for the long vowels, suggesting that they allocated more attentional resources to processing the speech in this task than the SLI group. This effect was only significant using the GFP analysis and was seen as smaller GFP for the TLD than SLI group. The SLI group also showed significantly later latency than the TLD group in reaching the maximum GFP. In addition, a significantly greater proportion of children with SLI compared to those with typical language showed left-greater-than-right frontocentral amplitude at the latency determined from each child’s maximum GFP peak. Conclusions Children generally showed greater attention to speech sounds when attention is directed to the auditory modality compared to the visual modality. However, children with TLD, unlike SLI, also appear to devote some attentional resources to speech even in a task in which they are instructed to attend to visual information and ignore the speech. Significance These findings suggest that children with SLI have limited attentional resources, that they are poorer at dividing attention, or that they are less automatic in allocating resources to speech compared to children with typically developing language skills.

We studied the effects of prolonged auditory deprivation in children in whom auditory stimulation was restored by a cochlear implant. The latency of the P1 component of the late cortical potential was used as the indicator of auditory system maturation. For normal-hearing children there is a gradual evolution of evoked potential features that extends through adolescence with P1 latency becoming adult-like at about age 15. It appears that maturation of P1 latency in normal and implanted children occurs at the same rate, but the time to maturity in implanted subjects is delayed by an amount approximately equal to the duration of deafness.

The aim of this study was to investigate mismatch negativity (MMN) responses to a variety of speech stimuli (/de:/, /ge:/, /deI/ "day", and /geI/ "gay") in a multiple deviant paradigm. It was hypothesized that all speech stimulus contrasts in the multiple deviant paradigm, including the fine acoustic speech contrast [d/g], would elicit robust MMN responses and that consonant vowel (CV) real word deviants (e.g., "day" and "gay") would elicit larger MMN responses than CV nonword deviants (e.g., "de" and "ge") within and across experimental contrasts.Ten healthy, right-handed, native English-speaking adults (23.4 +/- 2.27 yr) with normal hearing were presented with 12 blocks of stimuli, using a multiple deviant oddball paradigm. Each of the four speech stimuli were presented as standards (p = 0.7) in three blocks, with the remaining stimuli acting as deviants (p = 0.1 each). Subjects were also presented with the same stimuli in a behavioral discrimination task.MMN responses to the fine acoustic speech contrast [d/g] (e.g., "de" versus "ge", "day" versus "gay") did not reach significance. However, a significant and larger MMN response was obtained at an earlier latency to the real word deviants among nonword standards with the same initial consonant (i.e., de--day, ge--gay) when compared with the responses to nonword deviants among word standards (day--de, gay--ge).The results showed that MMN responses could be elicited by speech stimuli with large, single acoustic deviances, within a multiple deviant paradigm design. This result has positive clinical implications for the testing of subjects who may only tolerate short testing sessions (e.g., pathological populations) in that responses to a wider range of speech stimuli may be recorded without necessarily having to increase session length. The results also demonstrated that MMN responses were elicited by large, single acoustic deviances but not fine acoustic deviances within the speech stimuli. The poor results for the fine acoustic deviances support previous studies that have used single contrast paradigms and found that when carefully controlled methodological designs and strict methods of analysis are applied, robust responses to fine-grained CV syllable contrasts may be difficult to obtain. The enhanced MMN observed in response to the real word deviants among nonword standards may provide further evidence for the presence of long-term neural traces for words in the brain, however possible contextual effects limit the interpretation of these data. Further research is needed to investigate the ability of the MMN response to accurately reflect speech sounds with fine acoustic contrasts, as well as the ability of the MMN to reflect neural traces for words in the brain, before it can be reliably used as a clinical tool in the investigation of spoken word processing in pathological populations.

The purpose of this study was to compare the robustness of the event-related potential (ERP) response, called the mismatch negativity (MMN), when elicited by simple tone stimuli (differing in frequency, duration, or intensity) and speech stimuli (CV nonword contrast /de:/ vs. /ge:/ and CV word contrast /deI/ vs. /geI/). The study was conducted using 30 young adult subjects (Groups A and B; n = 15 each). The speech stimuli were presented to Group A at a stimulus onset asynchrony (SOA) of 610 msec and to Group B at an SOA of 900 msec. The tone stimuli were presented to both groups at an SOA of 610 msec. MMN responses were elicited by the simple tone stimuli (66.7%–96.7% of subjects with MMN "present," or significantly different from zero, p < 0.05) but not the speech stimuli (10% subjects with MMN present for nonwords, 10% for words). The length of the SOA (610 msec or 900 msec) had no effect on the ability to obtain consistent MMN responses to the speech stimuli. The results indicated a lack of robust MMN elicited by speech stimuli with fine acoustic contrasts under carefully controlled methodological conditions. The implications of these results are discussed in relation to conflicting reports in the literature of speech-elicited MMNs, and the importance of appropriate methodological design in MMN studies investigating speech processing in normal and pathological populations.

We acquired simultaneous high-field (3 T) functional magnetic resonance imaging (fMRI) and high-density (64- and 128-channel) EEG using a sparse sampling technique to measure auditory cortical activity generated by right ear stimulus presentation. Using dipole source localization, we showed that the anatomical location of the grand mean equivalent dipole of auditory evoked potentials (AEPs) and the center of gravity of fMRI activity were in good agreement in the horizontal plane. However, the grand mean equivalent dipole was located significantly superior in the cortex compared to fMRI activity. Interhemispheric asymmetry was exhibited by fMRI, whereas neither the AEP dipole moments nor the mean global field power (MGFP) of the AEPs showed significant asymmetry. Increasing the number of recording electrodes from 64 to 128 improved the accuracy of the equivalent dipole source localization but decreased the signal-to-noise ratio (SNR) of MR images. This suggests that 64 electrodes may be optimal for use in simultaneous recording of EEG and fMRI.

This study investigates the effects of profound acquired unilateral deafness on the adult human central auditory system by analyzing long-latency auditory evoked potentials (AEPs) with dipole source modeling methods. AEPs, elicited by clicks presented to the intact ear in 19 adult subjects with profound unilateral deafness and monaurally to each ear in eight adult normal-hearing controls, were recorded with a 31-channel system. The responses in the 70–210 ms time window, encompassing the N1b/P2 and Ta/Tb components of the AEPs, were modeled by a vertically and a laterally oriented dipole source in each hemisphere. Peak latencies and amplitudes of the major components of the dipole waveforms were measured in the hemispheres ipsilateral and contralateral to the stimulated ear. The normal-hearing subjects showed significant ipsilateral–contralateral latency and amplitude differences, with contralateral source activities that were typically larger and peaked earlier than the ipsilateral activities. In addition, the ipsilateral–contralateral amplitude differences from monaural presentation were similar for left and for right ear stimulation. For unilaterally deaf subjects, the previously reported reduction in ipsilateral–contralateral amplitude differences based on scalp waveforms was also observed in the dipole source waveforms. However, analysis of the source dipole activity demonstrated that the reduced inter-hemispheric amplitude differences were ear dependent. Specifically, these changes were found only in those subjects affected by profound left ear unilateral deafness.

Objectives : Previous studies have shown that observed patterns of auditory evoked potential (AEP) maturation depend on the scalp location of the recording electrodes. Dipole source modeling incorporates the AEP information recorded at all electrode locations. This should provide a more robust description of auditory system maturation based on age-related changes in AEPs. Thus, the purpose of this study was to evaluate central auditory system maturation based dipole modeling of multi-electrode long-latency AEPs recordings. Methods : AEPs were recorded at 30 scalp-electrode locations from 118 subjects between 5 and 20 years of age. Regional dipole source analysis, using symmetrically located sources, was used to generate a spatio-temporal source model of age-related changes in AEP latency and magnitude. Results : The regional dipole source model separated the AEPs into distinct groups depending on the orientation of the component dipoles. The sagittally oriented dipole sources contained two AEP peaks, comparable in latency to Pa and Pb of the middle latency response (MLR). Although some magnitude changes were noted, latencies of Pa and Pb showed no evidence of age-related change. The tangentially oriented sources contained activity comparable to P 1 , N 1b , and P 2 . There were various age-related changes in the latency and magnitude of the AEPs represented in the tangential sources. The radially oriented sources contained activity comparable to the T-complex, including Ta, and Tb, that showed only small latency changes with age. In addition, a long-latency component labeled TP 200 was observed. Conclusions : It is possible to distinguish 3 maturation groups: one group reaching maturity at age 6 and comprising the MLR components Pa and Pb, P 2 , and the T-complex. A second group that was relatively fast to mature (50%/year) was represented by N 2 . A third group was characterized by a slower pattern of maturation with a rate of 11–17%/year and included the AEP peaks P 1 , N 1b , and TP 200 . The observed latency differences combined with the differences in maturation rate indicate that P 2 is not identical to TP 200 . The results also demonstrated the independence of the T-complex components, represented in the radial dipoles, from the P 1 , N 1b , and P 2 components, contained in the tangentially oriented dipole sources.

Profoundly deaf children who use a cochlear implant (CI) provide a unique opportunity to investigate the effects of auditory sensory deprivation on the maturing human central nervous system. Previous results suggest that children fitted with a CI show evidence of altered auditory cortical maturation, based on evoked potentials. This altered maturation was characterized by both latency delays and morphological changes in the cortical auditory evoked potentials (AEPs). Based on prolonged P1 latencies compared to age-matched normal-hearing (NH) peers, these data suggested a delayed maturation nearly equivalent to the period of deafness. However, rates of maturation for this AEP peak were essentially the same in NH and CI children. This suggests that, given enough time, the AEPs of CI children would assume the characteristic morphology found in older NH teens and NH adults. However, the data also indicated a substantial alteration of the typical set of obligatory P1-N1b-P2 peaks, specifically related to the absence of the N1 potential. Recent analyses of more extensive sets of longitudinal and cross-sectional data indicate that even after many years of implant use, the AEPs of CI users in their late teens remain very different from those of their NH peers. The P1 peak latency remains prolonged and P1 amplitude remains much larger in CI users than in age-matched NH teens. These findings suggested that age-related changes in the P1 peak are completed by 12 years of age. In addition, the normal N1b peak fails to emerge in virtually all of the CI children tested in our laboratory. A major new interpretation of the abnormal maturation of AEP waveforms in CI children is presented. It is based on direct evidence showing that a persistent immaturity of the superficial layer axons has persistent negative effects on the generation of the N1b and, consequently, on the morphology of the AEPs. A comparison of scalp-recorded AEPs from implanted children with local field potentials measured from the cortical surface in deaf white kittens suggests the effects of deafness and CI use are similar across these mammalian species. For both species, a period of profound deafness followed by CI stimulation reveals a substantial immaturity in cortical activation even after a period of electrical stimulation by the CI.

Objective : The purpose of this study was to evaluate central auditory system maturation based on detailed data from multi-electrode recordings of long-latency auditory evoked potentials (AEPs). Methods : AEPs were measured at 30 scalp-electrode locations from 118 subjects between 5 and 20 years of age. Analyses focused on age-related latency and amplitude changes in the P 1 , N 1b , P 2 , and N 2 peaks of the AEPs generated by a brief train of clicks presented to the left ear. Results : Substantial and unexpected changes that extend well into adolescence were found for both the amplitude and latency of the AEP components. While the maturational changes in latency followed a pattern of gradual change, amplitude changes tended to be more abrupt and step-like. Age-related latency decreases were largest for the P 1 and N 1b peaks. In contrast, P 2 latency did not change significantly and the N 2 peak increased in latency as a function of age. Abrupt changes in P 1 , P 1 -N 1b , and N 2 peak amplitude (also RMS amplitude) were observed around age 10 at the lateral electrode locations C3 and C4, but not at the midline electrodes Cz and Fz. These changes in amplitude coincided with a sharp increase and plateau in AEP peak and RMS amplitude variability from 9 to 11 years of age. Conclusions : These analyses demonstrated that the observed pattern of AEP maturation depends on the scalp location at which the responses are recorded. The distinct maturational time courses observed for individual AEP peaks support a model of AEP generation in which activity originates from two or more at least partly independent central nervous system pathways. A striking parallel was observed between previously reported maturational changes in auditory cortex synaptic density and, in particular, the age-related changes in P 1 amplitude. The results indicate that some areas of the brain activated by sound stimulation have a maturational time course that extends into adolescence. Maturation of certain auditory processing skills such as speech recognition in noise also has a prolonged time course. This raises the possibility that the emergence of adult-like auditory processing skills may be governed by the same maturing neural processes that affect AEP latency and amplitude.

When auditory nerve function is lost due to surgical removal of bilateral acoustic tumors in cases of neurofibromatosis type 2, a sense of hearing may be restored by means of an auditory brainstem implant (ABI), which electrically stimulates the cochlear nucleus. Electrically evoked auditory brainstem responses recorded from ABI subjects exhibit a variety of waveforms due to the presence or absence of different components. Evidently, ABI stimulation activates different ascending auditory pathways in different individuals. This study examined whether such differences at the brainstem level are associated with corresponding differences at higher levels. Multichannel recordings of electrically evoked middle-latency and late auditory responses were obtained from two ABI subjects whose very different electrically evoked auditory brainstem responses represent distinct categories of waveform morphology. The waveforms of both types of response were qualitatively similar in that for each condition tested there were corresponding main peaks and troughs. Quantitatively, however, there were differences in the scalp distributions and magnitudes of all components present. One subject had distributions suggesting bilateral activation and an N1-P2 complex of large amplitude, whereas the other subject had distributions suggesting unilateral activation contralateral to the side of stimulation and an N1-P2 complex of small amplitude. The differences suggest that activation of different ascending pathways in the auditory system results in different spatial and temporal patterns of neural activity in the thalamic and/or cortical auditory areas.

If the repeated presentation of a single (standard) auditory stimulus is randomly interspersed with a second acoustically different (deviant) stimulus, the cortical activity evoked by the deviant stimulus can contain a negative component known as the mismatch negativity (MMN). The MMN is derived by subtracting the averaged response evoked by the standard stimulus from that evoked by the deviant stimulus. When the magnitude of the response is small or the signal-to-noise ratio is poor, it is difficult to judge the presence or absence of the MMN simply by visual inspection, and statistical detection techniques become necessary. A method of analysis is proposed to quantify the magnitude and statistically evaluate the presence of the MMN based on time-integrated evoked responses. This paper demonstrates the use of this integrated mismatch negativity (MMNi) analysis to detect the MMN evoked by stimulus contrasts near the perceptual threshold of two subjects. The MMNi, by virtue of being equivalent to a low-pass filtered response, presents an almost noise-free estimate of MMN magnitude. A single measure of the integrated evoked response at a fixed time point is used in a distribution-free statistic that compares the magnitude of the averaged response evoked by the deviant stimulus with a magnitude distribution derived from 200 subaveraged responses to the standard stimulus (with the number of sweeps per average equal to that of the deviant stimulus). This allows a calculation of the exact probability for the null hypothesis that the negative magnitude of the response evoked by the deviant stimulus is drawn from the magnitude distribution of responses evoked by the standard stimulus. Rejection of this hypothesis provides objective evidence of the presence of the MMN.

Deaf children fitted with a cochlear implant provide a unique opportunity to examine the effects of auditory deprivation on the maturation of the human auditory system. We compared cortical evoked potentials recorded in implanted and normal-hearing children and found that age-dependent latency changes for the P1 component, fitted to a decaying exponential curve, showed the same rate of maturation. For implanted children, however, maturational delays for P1 latency approximated the period of auditory deprivation prior to implantation. This indicates the auditory system does not mature without stimulation. Nonetheless, the auditory system retains its plasticity during the period of deafness since the re-introduction of stimulation by the cochlear implant resumes the normal maturational sequence.

Objective: We investigated maturation of cortical auditory function in normal-hearing children and in children who receive stimulation of their auditory system through a cochlear implant. Design: As a measure of cortical auditory function, auditory evoked responses (AERs) were recorded from normal-hearing children and adults as well as from children and adults fitted with a cochlear implant. Morphological and latency changes for evoked responses recorded at electrode Cz are reported. Results: For normal-hearing children, there is a gradual evolution of AER features that extends through adolescence, with P 1 latency becoming adult-like in the late teens. Latency changes for P 1 occur at the same rate for implanted children, but the overall maturation sequence is delayed. By extrapolation from the existing data, the age at which P 1 latency becomes adult-like is delayed by approximately 5 yr for the implanted population. Other typical features of the AER, namely N 1 and P 2 , are either delayed in developing or absent in the implanted children. Conclusions: These preliminary findings suggest both similarities and differences in cortical auditory maturation for normal-hearing and implanted children. For implanted children, the 5 yr delay for maturation of P 1 latency roughly corresponds to the average 4.5 yr interval between the onset of deafness and the time of implantation. These findings suggest that during the period of deafness, maturation of cortical auditory function does not progress. However, some, if not all, maturational processes resume after stimulation is reintroduced.

In attempting to correlate developmental anatomical data with electrophysiological data on maturation of the auditory brain stem response (ABR), a model of ABR generation was necessary to match neuroanatomical structures to ABR components. This model has been developed by reviewing quantitative studies of human brain stem nuclei, results of intrasurgical recordings, studies of correlation of pathology with ABR waveform alterations, and findings from direct stimulation of the human cochlear nuclei through a brain stem implant device. Based on this material, it was assumed that waves I and II are generated peripherally in the auditory nerve and that waves III, IV, and V are generated centrally, i.e., by brain stem structures. It was further assumed that wave III is generated by axons emerging from the cochlear nuclei in the ventral acoustic stria and that waves IV and V reflect activity in parallel subpopulations of these ascending axons at a higher brain stem level. Beyond the cochlear nucleus, the largest component of the brain stem auditory pathway consists of axons projecting without interruption from the cochlear nuclei to the contralateral lateral lemniscus and inferior colliculus. In the proposed model of ABR generation, the III-IV interwave interval is assumed to reflect only axonal conduction in this asynaptic pathway. Electrophysiological data from infants indicate that the III-IV interwave interval becomes adult-like by the time of term birth. The second largest component of the brain stem auditory pathway is the bilateral projection through the medial olivary nucleus. The model assumes that activity in this monosynaptic pathway, consisting of axonal conduction time plus one synaptic delay, is reflected in the III-V interwave interval. If both of the preceding assumptions are true, the IV-V interwave interval represents the difference between the two pathways, i.e., the time of transmission across one synapse. The electrophysiological ABR data indicates that the IV-V interval does not mature until one year of age. It is also possible to apply this model to the peripherally generated portion of the ABR. The I-II interwave interval, assumed to solely represent conduction in VIIIth nerve axons, is adult-like before the time of term birth. The II-III interval, presumed to contain a synapse in the cochlear nuclear complex, does not reach an adult level until between 1 and 2 yr postnatal age.

Objective: To determine whether the source of age-dependent latency changes for ABR wave I results from cochlear mechanics or the haircell-neuron synapse. Design: Cochlear traveling wave delays were estimated on the basis of derived ABR response latencies and DPOAE phase delays. The difference in travel time between adjacent one octave-separated frequencies was calculated for four age groups: 30 to 33 wk old, 34 to 37 wk old, 38 to 42 wk old (term), and young adults. Results: We found that there were essentially no travel time differences between newborns in the 34 to 37 and the 38 to 42 wk conceptional age (CA) groups as estimated from DPOAE phase delays. For the 30- to 33-wk-olds, DPOAE travel times were increased at all frequencies, likely due to mild (about 10 to 15 dB) conductive hearing losses. Differences in travel times between adjacent bands, however, were not different from the other neonatal groups. Estimates on basis of wave I latency showed delays for the high-frequency region, 6 to 11 1 kHz, that were still immature at term. Conclusions: A comparison of frequency-dependent travel times calculated for wave I and DPOAE data in comparable age groups suggests mature cochlear functioning at 35 wk CA and a delayed maturation for the haircell-auditory nerve synapses relative to the preneural components for the basal turn with center frequencies above 6 kHz.

Objective: The goal of this study was to correlate developmental data on brain stem auditory path length with data on auditory brain stem response (ABR) conduction time. This was done to estimate changing axonal conduction velocity during the perinatal period. Design: Pathway length was determined by three-dimensional reconstruction of postmortem fetal and infant brain stems in an AutoCAD system. Brain stem conduction time was obtained from previous ABR studies of premature, term, and post-term infants. The process of correlation of path length and conduction time was based on a model of ABR generation (Ponton, Moore, & Eggermont, this issue) that assumes that the III-IV interpeak interval represents activity in an asynaptic pathway and, thus, consists of only axonal conduction time. Results: Brain stem conduction time is adult-like by the time of term birth. However, the brain stem auditory pathway continues to lengthen postnatally, with portions of the pathway not reaching adult dimensions until 3 yr of age. We determined lengths at various perinatal ages for three different segments of the auditory pathway. Each segment began at the cochlear nucleus (site of wave III generation) and ended at a more rostral location that is a possible site of wave IV generation. Conduction velocity was estimated by dividing path length by axonal conduction time (III-IV interpeak interval). All three assumed sites of generation of wave IV gave estimates of a threefold increase in conduction velocity between 29 wk CA and adult-hood. However, three highly discrepant measures of absolute conduction velocity were obtained for the different path segments. The most reasonable conduction velocity estimates, from 5 m/sec at 29 wk conceptional age to 20 m/sec in adults, were produced by assuming a site of generation for wave IV near the contralateral medial superior olivary nucleus. Conclusions: Prenatally, increasing conduction velocity more than compensates for increasing path length, causing ABR conduction time to decrease. Postnatally, increasing conduction velocity exactly compensates for increasing path length while ABR conduction time remains stable. Different aspects of myelin development may underlie these two phenomena.

For individuals with severe or profound hearing loss, electrical stimulation of surviving neural elements by a cochlear implant may partly restore a sensation of hearing. Determining the extent of restoration based on behavioral measures may be difficult, particularly when evaluating young children or individuals who have little or no experience with normal hearing. In normal-hearing individuals, an objective measure of sound discrimination may be obtained by studying the mismatch negativity (MMN) component of the auditory evoked potential. The MMN may be evoked by a number of physical differences in acoustic stimuli including duration and pitch. For cochlear implant users, analogous stimulus differences may be produced by changing the length of a stimulus pulse train or by changing the pair of activated electrodes along a multi-electrode implant array. This paper will provide an overview of our current results, comparing evoked response data recorded from both normal-hearing individuals and cochlear implant users. In both normal-hearing individuals and cochlear implant users, MMNs were evoked by differences in stimulus train duration and pitch (or electrode pair activation in cochlear implant users). These findings suggest that the MMN may be a useful method for assessing the discriminability of electrical stimulation patterns produced by a cochlear implant. Eventually, information gained by MMN testing may yield important information for developing rehabilitation programs for the individual user.

In developmental populations, durations of auditory brain‐stem response (ABR) I–III, III–V, and I–V vary substantially across individuals, particularly among preterm infants. Adult ABR interpeak latency has a strong correlation with brain‐stem size and weaker correlation with head size. To determine if head size might contribute to this increased interpeak latency variability among infants, ABR data were normalized based on head circumference. Normalization by head circumference did not reduce interpeak variability. Further analyses revealed a negative correlation between interpeak latency and head circumference that varied as a function of age. Before 42 weeks conceptional age (CA), a significant relation exists between increased head circumference and decreased duration of the III–V and I–V intervals, but not the I–III interval. For infants older than 42 weeks CA, there was a significant relation between increased head circumference and decreased duration for the I–III intervals but not the III–V and I–V intervals. An age‐dependent correlation between decreasing interpeak latency and increasing head circumference suggests that improved neural transmission through the auditory nerve and brain‐stem pathway offset or even overcompensate for developmental lengthening of the sensory pathway. Also, developmental time constants obtained from nonlinear curve fit analyses were shorter for normalized than non‐normalized data, particularly for the I–V interval. Therefore, correction of ABR data for the length of the sensory pathway may be important to estimate accurately maturation rate for developmental populations.

Previous studies of human auditory development using frequency‐specific auditory brain‐stem responses (ABRs) have reported that maturation for both peak and interpeak latencies occurs earlier for responses generated by low‐frequency stimuli. In two of these studies, low‐frequency ABRs presumed to originate from apical locations in the cochlea were likely dominated by activity from higher frequency regions closer to the base. In the present study, the high‐pass noise‐masking technique was used to generate derived ABRs that represent activity from isolated place specific regions along the basilar membrane. Analysis of auditory brain‐stem maturation based on I–V interpeak latency differences with adult means revealed a frequency‐specific pattern of development. Developmental changes occurred faster and mature function was attained earlier for ABRs from the mid‐center‐frequency (CF) derived conditions than from either the highest or lowest CF derived conditions. The differential maturation of mid‐CF derived ABRs may reflect the delayed effects of the pattern of development that occurs in the cochlea.

The maturation of the traveling-wave delay in the human cochlea was investigated in 227 subjects ranging in age from 29 weeks conceptional age to 49 years by using frequency specific auditory brain-stem responses (ABRs). The derived response technique was applied to ABRs obtained with click stimuli (presented at a fixed level equal to 60-dB sensation level in normal hearing adults) in the presence of high-pass noise masking (slope 96 dB/oct) to obtain frequency specific responses from octave-wide bands. The estimate of traveling-wave delay was obtained by taking the difference between wave I latencies from adjacent derived bands. It was found that the traveling-wave delay between the octave band with center frequency (CF) of 11.3 kHz and that with CF of 5.7 kHz decreased (about 0.4 ms on average) in exponential fashion with age to reach adult values at 3-6 months of age. This decrease was in agreement with reported data in kitten auditory-nerve fibers. The traveling-wave delays between adjacent octave bands with successive lower CF did not change with age.

The anatomical development of the human cochlea starts in the middle basal turn and progresses both toward the base and the apex. Behavioral responses, in contrast, appear to emerge for lower frequencies first. Cochlear tuning may continue to change during early development and so effect electrophysiological and behavioral measures of maturation. The maturation of the cochlear traveling wave delay as well as the ABR I-V interval was investigated using the derived response technique which permits a frequency dependent analysis of this maturation. It was found that the traveling wave delay decreased significantly with age for the most basal part of the cochlea; however, it was not affected by age for more apical locations. The I-V delay difference with the adult values was found significantly shorter in the derived octave band with CF = 2.8 kHz than in all other bands for the preterm, term and infant groups. This suggests that the frequency dependent electrophysiological maturation of the brainstem parallels the anatomical development of the cochlea.

In a diagnostic system wherein a patient's auditory brainstem response (ABR) to each of a plurality of auditory stimuli is recorded and wherein a plurality of derived-band ABRs representing cochlear responses in a plurality of respective frequency bands are constructed, the derived-band ABRs are temporarily aligned based on observable peaks in integrated, detrended derived-band waveforms.

Cortical activity reflected in auditory‐evoked potentials (AEPs) is often evaluated using only a small subset of all the recorded data. Conclusions based on this approach can be misleading, with no utility in identifying the underlying neural generators of the scalp recorded activity. Techniques that make use of all of the AEP data range from relatively simple methods, such as global field power, to more advanced approaches including independent components analysis (ICA), dipole modeling, and current density reconstruction. The objective of this presentation is to describe analysis of the component‐structure of AEPs using these advanced techniques. Results of the ICA analysis will be used to generate spatial filters characterizing the specific scalp distribution associated with each ICA pattern. The cortical origin of each ICA scalp distribution will then be determined using current density reconstruction. The analysis will be applied to standard AEPs as well as the mismatch negativity in normal hearing and cochlear implant users. The results will demonstrate the unique suitability of neuroimaging based on AEPs for understanding the effects of cochlear implant use on cortical activity associated with cognitive processing in children and in adults.

The understanding of spoken language development has been expanded by examining speech‐sound evoked brain activity recorded using an oddball presentation paradigm. When brain activity is recorded using this paradigm, a response known as the mismatch negativity (MMN) is generated. The MMN is regarded as a neurophysiological correlate of short‐term auditory memory processes that are necessary for behavioral discrimination. Numerous investigations have demonstrated that neural generators underlying the MMN are sensitive to a wide range of acoustic contrasts, including both nonspeech and speech sounds. Recent studies have shown that for at least some speech sound contrasts, the MMN is present at birth and is insensitive to native/non‐native speech contrasts. The appearance of language‐specific contrasts around six months of age appears to correspond with the emergence of myelinated connections between the thalamus and auditory cortex. Combined, the neurophysiological and anatomical data suggest that this neur...

Auditory‐evoked responses provide detailed, objective measures of maturational change in the central auditory system from the level of the brainstem to the cortex. Auditory‐evoked responses can reflect activity originating from three pathways: the lemniscal and nonlemniscal pathways as well as from a modality nonspecific pathway originating in the reticular activating system (RAS) and its associated thalamic nuclei. Maturational time courses for these pathways were derived from evoked response data recorded from 156 normal‐hearing subjects ranging from 5–20 years of age. Analyses of these data indicate that each pathway may have a unique developmental sequence. For normal‐hearing children, the lemniscal pathway appears to follow a longer developmental time course than either the nonlemniscal or RAS pathways. For children with implants, the developmental sequences for these pathways are differentially affected depending on onset and duration of deafness. Specifically, maturation of the lemniscal pathway is...

Dichotic stimulation, the simultaneous presentation of two different acoustic signals to the right and left ears, respectively, is used routinely in the clinical assessment of speech lateralization as well as in other central auditory testing procedures in the clinic and laboratory. At present, most researchers and clinicians depend on a few commercial sources for dichotic tapes, because there are a limited number of facilities which are able to produce such tapes. Moreover, some of the commerical tapes currently offered for sale contain important stimulus errors. In the present paper, we describe a general set of programs for the PDP 11 series of computers, which permits sequences of dichotic stimuli to be generated and output with a high degree of precision. These programs therefore allow researchers to generate any desired sequence of dichotic stimulation, for recording and taping, for use in their research. The programs operate in two stages to generate the required dichotic sequences. In the first stage, the constrained random ordering of the stimuli is generated as specified by the user. In the second stage, after the preliminary stimulus preparation has been completed (for example, using a waveform editing package; cf., D. G. Jamieson and D. A. Naugler, Comput. Biomed. Res., 1985, 18, 480), an audio tape is generated with stimuli presented dichotically, with timing and sequencing precisely as specified.