Curtis W. Ponton

Maturation of human central auditory system activity : evidence from multi-channel evoked potentials

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 P1, N1b, P2, and N2 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 P1 and N1b peaks. In contrast, P2 latency did not change significantly and the N2 peak increased in latency as a function of age. Abrupt changes in P1, P1-N1b, and N2 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 P1 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.

Central auditory plasticity: changes in the N1-P2 complex after speech-sound training.

Objective To determine whether the N1-P2 complex reflects training-induced changes in neural activity associated with improved voice-onset-time (VOT) perception. Design 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). Results 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. Conclusions 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.

Maturation of human central auditory system activity: separating auditory evoked potentials by dipole source modeling

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 P1, N1b, and P2. 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 TP200 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, P2, and the T-complex. A second group that was relatively fast to mature (50%/year) was represented by N2. A third group was characterized by a slower pattern of maturation with a rate of 11-17%/year and included the AEP peaks P1, N1b, and TP200. The observed latency differences combined with the differences in maturation rate indicate that P2 is not identical to TP200. The results also demonstrated the independence of the T-complex components, represented in the radial dipoles, from the P1, N1b, and P2 components, contained in the tangentially oriented dipole sources.

Maturation of human cortical auditory function : Differences between normal-hearing children and children with cochlear implants

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 P1 latency becoming adult‐like in the late teens. Latency changes for P1 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 P1 latency becomes adult‐like is delayed by approximately 5 yr for the implanted population. Other typical features of the AER, namely N1 and P2, 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 P1 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.

Auditory system plasticity in children after long periods of complete deafness

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 P1component, 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.

Auditory-evoked potential studies of cortical maturation in normal hearing and implanted children: correlations with changes in structure and speech perception.

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.

The Neurophysiology of Auditory Perception: From Single Units to Evoked Potentials

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.

Auditory brain stem response generation by parallel pathways : Differential maturation of axonal conduction time and synaptic transmission

&NA; 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.

Plasticity in the adult human central auditory system: evidence from late-onset profound unilateral deafness.

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.

Maturation of the Mismatch Negativity: Effects of Profound Deafness and Cochlear Implant Use

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.