Manuel Don

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.

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.

Effect of Click Rate on the Latency of Auditory Brain Stem Responses in Humans

Auditory brain stem responses are the far-field reflections of electrical activity originating in the auditory pathway in its course from the cochlea to cortex that can be recorded from scalp electrodes using computer averaging techniques. There are seven components in the initial 10 msec following a click signal which have been shown to have an orderly change in latency as a function of signal intensity. The results of this study show that click repetition rate can also significantly affect the response latency measure. Responses were measured in six normal hearing subjects at click rates of 10, 30, 50, and 100/sec and at four intensity levels (30, 40, 50, and 60 dB sensation level). The mean latency shift of component V was approximately 0.5 msec when the responses at 10 and 100/sec were compared. This is equivalent to a 15–20 dB decrease in signal intensity at the 10/sec click rate. An analysis of the time of occurrence of this shift using brief click trains at 100/sec showed the shift in latency to be complete by the fifth click. The latency shift was similar at the four signal levels tested. The latency shift of component V appeared to be a monaural and therefore a potentially peripheral process. The results are interpreted as an objective measure of adaptation in the human auditory system with implications for the measurement in disorders of hearing.

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.

Auditory steady-state responses to chirp stimuli based on cochlear traveling wave delay.

This study investigates the use of chirp stimuli to compensate for the cochlear traveling wave delay. The temporal dispersion in the cochlea is given by the traveling time, which in this study is estimated from latency-frequency functions obtained from (1) a cochlear model, (2) tone-burst auditory brain stem response (ABR) latencies, (3) and narrow-band ABR latencies. These latency-frequency functions are assumed to reflect the group delay of a linear system that modifies the phase spectrum of the applied stimulus. On the basis of this assumption, three chirps are constructed and evaluated in 49 normal-hearing subjects. The auditory steady-state responses to these chirps and to a click stimulus are compared at two levels of stimulation (30 and 50 dB nHL) and a rate of 90s. The chirps give shorter detection time and higher signal-to-noise ratio than the click. The shorter detection time obtained by the chirps is equivalent to an increase in stimulus level of 20 dB or more. The results indicate that a chirp is a more efficient stimulus than a click for the recording of early auditory evoked responses in normal-hearing adults using transient sounds at a high rate of stimulation.

Gender differences in cochlear response time: An explanation for gender amplitude differences in the unmasked auditory brain‐stem response

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.

Maturational Delays in Cortical Evoked Potentials in Cochlear Implant Users

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.