Betty Kwong

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.

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.

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.

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.

Maturation of human central auditory system activity: the T-complex

OBJECTIVE The purpose of this study was to evaluate and describe the maturation of a set of auditory evoked potentials (AEPs) described as the T-complex from a large group of children, adolescents, and young adults who ranged in age from 5 to 20 years of age. METHODS The AEPs evoked by brief trains of clicks presented to the left ear were measured at 30 scalp-electrode locations. Analyses focused on age-related latency and amplitude changes in the T-complex recorded at the temporal electrode sites T3 and T5 over the left hemisphere and T4 and T6 over the right hemisphere. The maturation of the T-complex components Na, Ta, and Tb was contrasted with those of the obligatory AEPs P1, N1b, and P2 measured at electrodes C3 and C4. RESULTS T-complex activity was present in the grand average AEPs of all 14 age groups spanning ages 5-20 years. T-complex components recorded at electrodes T3 and T4 differed in both morphology and maturation rate from those recorded at T5 and T6. In contrast to the prolonged maturation of AEP latency measured at electrodes T5 and T6, the T-complex components measured at electrodes T3 and T4 did not show a significant overall change in peak latency as a function of age. Consistent amplitude and latency correlations were found between the obligatory AEP components P1, N1b and P2 recorded at C3 and C4 and the T-complex components measured at T5 and T6, but not T3 and T4. CONCLUSIONS Distinct patterns of AEP maturation were measured at electrode sites commonly used to record the T-complex. At scalp electrodes located over more posterior temporal areas (T5 and T6), the AEPs were characterized by a prolonged pattern of maturation very similar to that measured at the central electrodes C3 and C4. These findings and others reported in this paper provide strong evidence that the AEPs recorded at electrodes T5 and T6 are not T-complex peaks. In contrast, the AEPs measured at electrodes T3 and T4 over more anterior temporal scalp areas appear largely independent of activity measured at the central electrode locations. The T-complex peaks Ta and Tb measured at these scalp locations mature early, with no overall significant age-related changes in peak latencies. SIGNIFICANCE The T-complex is recorded from the temporal electrodes T3 and T4 represents activity of secondary auditory cortex better than, and independent from, midline potentials. Its robust presence in 5-8 year olds supports its potential usefulness in assessing language impairment.

Differential Ear Effects of Profound Unilateral Deafness on the Adult Human Central Auditory System

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.

A diagnostic test for Ménière's Disease and Cochlear Hydrops: impaired high-pass noise masking of auditory brainstem responses.

Hypothesis: Endolymphatic hydrops in patients diagnosed with Ménières disease causes changes in the response properties of the basilar membrane that lead to impaired high-pass noise masking of auditory brainstem responses to clicks. Background: Ménières disease is defined as the idiopathic syndrome of endolymphatic (cochlear) hydrops, which is an abnormal increase in the volume of cochlear fluid (endolymph) in the inner ear. Accurate detection and diagnosis are important but difficult because of the lack of sufficiently sensitive tests. Methods: Two populations were compared: (1) 38 non-Ménières normal-hearing subjects; and (2) 23 patients who, at the time of testing, continued to have at least three of the four hallmark symptoms (i.e., tinnitus, vertigo, fluctuating hearing loss, and fullness) used in the diagnosis of Ménières disease. Auditory brainstem responses to clicks presented ipsilaterally with masking noise that was high-pass filtered at various frequencies were recorded. Results: In the Ménières patients, the masking noise is insufficient such that an undermasked Wave V is still present at a latency similar to that of Wave V in the response to the clicks alone. In the control non-Ménières normal-hearing subjects, this undermasked component was either absent or significantly delayed because of the masking noise. The difference in the delays between these populations is such that the distributions do not overlap, resulting in 100% sensitivity and 100% specificity. Conclusion: This test is able to distinguish objectively active Ménières disease in individuals and may show promise for tracking changes in the severity of the disease caused by progression or treatment.

The effects of sensory hearing loss on cochlear filter times estimated from auditory brainstem response latencies

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 Vs 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.