Flint A. Boettcher

Auditory evoked potentials in aged gerbils: responses elicited by noises separated by a silent gap

The compound action potential (CAP) and the auditory brainstem response (ABR; waves ii and iv) were recorded in young (4-8 month) and aged (33-37 month) gerbils using a paradigm similar to that used in some psychophysical studies of gap detection (a pair of identical low-pass noises separated by a silent gap). Response amplitudes were analyzed in terms of absolute amplitudes and the amplitude ratio (the amplitude of the response to the second noise of a pair divided by that to the first). Response latencies were analyzed in terms of the absolute latencies as well as the latency shift (the latency of the response to the second noise minus that to the first). Response amplitudes were much smaller in the aged subjects for both the first and second stimuli of a pair. There were minimal changes in amplitude ratios across age for both the CAP and ABR. Absolute latencies were similar between groups for the first stimulus of a pair, but latencies to wave iv were much longer for the aged subjects when the gap was short. Thus, the latency shift for the aged group was much longer for wave iv in the aged compared to the young group, but were similar between groups for the CAP or wave ii of the ABR. The results suggest that there may be changes in coding of temporal information in the auditory brainstem of aged gerbils which are not a direct result of abnormal temporal processing in the auditory periphery.

Age-related changes in auditory evoked potentials of gerbils. I. Response amplitudes.

Auditory brainstem responses (ABRs) were recorded in young (6-10 month) and aged (36 month) Mongolian gerbils. For each subject, ABR thresholds and response amplitudes were measured at octave intervals from 1 through 16 kHz. Data from the young animals served as the baselines for comparison to aged animals which were categorized on the basis of auditory brainstem response (ABR) thresholds. The aged groups included subjects with thresholds (a) at the mean of a pool of 50 aged gerbils, (b) one standard deviation (SD) lower than the mean, (c) one sd higher than the mean, and (d) near normal for young gerbils. The amplitudes of ABR waveforms for the aged gerbils were reduced compared to the young subjects, particularly at high sound pressure levels. This was true even for aged subjects with thresholds similar to those for younger subjects. The slopes of the amplitude-intensity (I/O) functions were shallower in all aged subjects compared to young subjects. The results suggest that ABR amplitudes and I/O slopes decrease as a function of age and that the decreases are not a direct result of loss of auditory sensitivity. The reductions in ABR amplitudes from aged gerbils presumably reflect age-related pathology in the auditory periphery, as previous studies have shown reductions in amplitudes of the compound action potential of aged gerbils.

Decline in the endocochlear potential corresponds to decreased Na,K-ATPase activity in the lateral wall of quiet-aged gerbils

The ion transport-mediating enzyme, Na,K-ATPase, is abundantly present in the cochlear lateral wall. This enzyme is essential for the generation and maintenance of the endocochlear potential. Diminished enzyme activity has been observed previously in the lateral wall of quiet-aged gerbils. The present study was designed to investigate the impact of the age-related decline in Na,K-ATPase specific activity upon auditory function. Measures of the resting endocochlear potential value and the level of Na,K-ATPase specific activity were made in cochleae obtained from gerbils aged in quiet conditions. Analysis revealed a high degree of correspondence between the level of lateral wall Na,K-ATPase specific activity and the value of the endocochlear potential measured in the round window/turn 1 region of the cochlea. Nonlinear regression models showed a strong relationship between the age-related reductions in enzyme activity and the magnitude of the endocochlear potential. The data suggest that during metabolic presbyacusis a decrease in Na,K-ATPase specific activity can explain most, but not all, of the decline in the endocochlear potential.

The amplitude-modulation following response in young and aged human subjects

The amplitude-modulation following response (AMFR) is a steady-state auditory response which may be an objective measure of intensity discrimination. Aged subjects with normal hearing have poorer intensity discrimination for low-frequency tones measured behaviorally, which would predict poorer AMFRs for low-frequency carriers. Experiment 1 was designed to assess age-related differences in AMFR characteristics. Response amplitudes were not significantly different among the young and aged groups for either carrier frequency (520 or 4000 Hz) or modulation depth (0--100%). Response phase did not vary systematically among groups. These results suggest that the AMFR may not be directly comparable to behavioral measures of intensity discrimination in aged subjects with normal hearing. To assess the contribution of high-frequency hearing loss on the AMFR in aged subjects, Experiment 2 compared AMFR amplitudes in aged subjects and in young subjects under the condition of high-pass masking. The amplitude of the AMFR was reduced at 520 Hz for both aged subjects and masked young subjects compared to unmasked young subjects, suggesting that reduced amplitudes in aged subjects with high-frequency hearing loss were associated with threshold elevations. Furthermore, the results suggest that the base of the cochlea contributes to the AMFR for low carrier frequencies.

Age-related changes in auditory evoked potentials of gerbils. II. Response latencies

Auditory brainstem responses (ABR) were recorded in young (6-10 month) and aged (36 month) Mongolian gerbils. Data from the young animals served as the baselines for comparison to aged animals which were categorized on the basis of ABR thresholds. Aged gerbils with normal thresholds (re young controls) had wave i and ii latencies of the ABR which were relatively normal at 1-4 kHz and slightly reduced at 8 and 16 kHz. Wave iv latencies in the aged gerbils with normal thresholds were reduced at all frequencies. Aged gerbils with 10-30 dB of hearing loss had wave i, ii, and iv latencies which were prolonged at low sound pressure levels and normal at high stimulus levels. Aged gerbils with 30 dB or greater losses had prolonged wave i, ii, and iv latencies at most levels. Slopes of latency-intensity (L/I) functions were steeper at 1-4 kHz than controls in aged subjects with hearing losses of 10 dB or greater. Slopes of L/I functions for wave iv were normal in aged subjects. The wave i-iv interval was shorter than normal in aged subjects with no hearing loss, normal in aged subjects with 10-30 dB of loss, and prolonged in subjects with greater than 30 dB of loss.

Auditory brainstem responses in younger and older adults for broadband noises separated by a silent gap

Wave V of the auditory brainstem response was measured to two 50-ms broadband noise bursts separated by silent gaps of varied duration (4, 8, 32, or 64 ms) for younger and older adults with normal hearing. All subjects had measurable wave V responses to the first noise burst. However, for the second noise burst, three of eight older adults did not have responses with gap durations of 4 and 8 ms, and one of eight younger adults did not have a measurable response with a gap duration of 4 ms. When responses were present for older adults, latencies were similar to those of younger subjects but amplitudes were smaller. These results suggest age-related deficits in gap detection at the level of the brainstem in a group of aged subjects with no threshold elevation. Results are similar to those of Boettcher et al. (1996) using an identical paradigm in young and aged Mongolian gerbils.

Behavioral and evoked-potential thresholds in young and old Mongolian gerbils (Meriones unguiculatus)

Age-dependent hearing loss has been well documented in gerbils exceeding 2 years of age using physiological methods (e.g. [Mills et al. (1990) Hear. Res. 46, 201-210]). We determined behavioral thresholds for broad-band noise and pure-tone pulses in gerbils as a function of age. Contrary to expectations based on previously published physiological data, we found no significant (broad-band noise and 10 kHz) or only a very small hearing loss (7 dB at 2 kHz) in 30-36-month-old animals. In animals over 3 years of age we observed an increased spread of thresholds and threshold shifts exceeding 20 dB in some individuals. Behavioral thresholds of old gerbils from two breeding colonies (University of Regensburg and Medical University of South Carolina) were similar. Data from individual animals where thresholds were determined physiologically and behaviorally indicate that results from auditory brainstem response measurements show no shift at 18 months while subsequent measurements at 28-29 months revealed age-dependent threshold shifts of 10-15 dB. In contrast, thresholds determined by behavioral methods in these same individuals at 31-33 months of age remained stable.

The frequency-modulation following response in young and aged human subjects

The frequency-modulation following response (FMFR) is a steady-state evoked response which may be a neural correlate of frequency discrimination. Aged subjects with normal hearing have abnormal frequency discrimination for low carrier frequencies and thus it might be predicted that aged individuals would have reduced FMFR amplitudes compared to young subjects. In this study, FMFR amplitudes were measured for frequency-modulated sinusoids with a carrier frequency of 0.5 kHz (80 dB SPL). In Experiment 1, the modulation depth was held constant (80%) and the modulation rate was varied (4-38 Hz), whereas in Experiment 2 the modulation rate was held constant (38 Hz) and the modulation depth was varied (0-80%). Aged subjects had significantly larger FMFR amplitudes than young subjects for certain stimulus parameters, although individual variability was large. Such results would not be predicted given previous data regarding frequency discrimination, but are consistent with several reports of larger-than-normal amplitudes of middle latency and late responses in aged subjects.

Effects of nimodipine on noise-induced hearing loss.

The effects of nimodipine, a calcium channel blocker, on noise-induced hearing loss were examined in gerbils. Animals were implanted subcutaneously with a timed-release pellet containing either nimodipine (approximately 10 mg/kg/day) or placebo and exposed to either 102 or 107 dBA noise. Serum levels were tested in two subjects and were in the range known to protect humans from cerebral artery vasospasm and ischemia-related neurologic deficits. Nimodipine and control groups had similar amounts of noise-induced (a) permanent threshold shift; (b) reductions in distortion product otoacoustic emissions; (c) reductions in tuning and suppression of the compound action potential; and (d) loss of outer hair cells. The results suggest that nimodipine, at a dose which results in clinically relevant serum levels, does not provide protection from the effects of moderately intense noise exposures.

Masking of auditory brainstem responses in young and aged gerbils

Auditory brainstem responses (ABR) were recorded in the presence of low-pass (1 kHz cutoff) or high-pass (8 kHz cutoff) filtered noise in young (4-8 month) and aged (36 month) gerbils. For low-pass maskers, aged gerbils had higher masked thresholds at 2 and 4 kHz than young subjects. This was true for all aged subjects, including those with quiet thresholds similar to those of young controls. For high-pass masking, the majority of aged subjects had higher masked thresholds at 2 and 4 kHz than young controls; however, aged subjects with relatively normal quiet thresholds had masked thresholds similar to those of young subjects. A modified power-law (MPL) model was used to predict masked thresholds for aged subjects. Thresholds measured in the presence of low-pass noise were higher than predicted in many of the aged subjects, particularly those with near-normal quiet thresholds. In contrast, thresholds measured in the presence of the high-pass masker were similar to the predicted thresholds. These results suggest that: (a) excess masking occurred in aged subjects for low-pass, but not high-pass, maskers; (b) the excess masking occurred independently of quiet thresholds; and (c) excess upward spread of masking was related to the spectrum of the masker and not the 2 and 4 kHz regions of the auditory periphery.