Cochlear implantation of auditory neuropathy.

Auditory neuropathy (AN) is a hearing disorder that presents with a grossly abnormal or absent neural response as measured by evoked potentials in the presence of normal outer hair cell function evidenced by present otoacoustic emissions or cochlear microphonics. Rehabilitation for patients with AN is challenging due to abnormal temporal encoding at the auditory nerve leading to severely impaired speech perception. Although patients with AN may demonstrate improvement in thresholds with amplification, temporal encoding dysfunction, and consequently speech perception degradation, is not alleviated by amplification. Another issue is the heterogeneity of the AN population in terms of audiologic and neurologic findings, in addition to uncertain etiology and pathophysiology. For children with prelingual onset of AN, development of auditory and oral communication skills is particularly compromised. All children with hearing loss in the severe-to-profound range who do not benefit from conventional amplification can be considered candidates for a cochlear implant (CI). This paper presents a case study of a child with AN who received a CI. Whereas no synchronous neural response auditory brainstem response could be elicited to acoustic stimuli, an electrically evoked auditory nerve action potential was evident following implantation, suggesting restoration to some degree of neural synchrony. Significant improvement in speech perception was found post-CI. Recommendation to implant all patients with AN would be premature, but these findings suggest that electrical stimulation in some cases of auditory neuropathy can be a viable option.

Regenerated hair cells become functional during continuous administration of kanamycin.

The compound action potential (CAP) was used to assess the functional status of regenerated hair cells in the chick cochlea during prolonged administration of kanamycin (KM). Immediately after 10 days of KM treatment, the CAP thresholds were elevated by 6-54 dB above those from age-matched control animals. The frequencies with the greatest threshold shifts (> 1 kHz) corresponded to the hair cell lesion in the basal 40% of the basilar papilla. After 20 days of KM, the CAP thresholds at 3 and 4 kHz were significantly lower than those after 10 days of KM treatment, but virtually the same as those after 10 days of KM plus 10 days of recovery. Similarly, the CAP amplitudes at frequencies higher than 1.5 kHz were significantly greater in animals that received KM for 20 days than in animals that received KM for 10 days. The threshold as well as amplitude improvement between 10 days and 20 days of KM treatment was associated with the morphological maturation of the regenerated hair cells in the basal 25% of the cochlea. In addition, the rapid functional recovery seen at high frequencies coincided with the base-to-apex gradient of morphological recovery in the basilar papilla. These results suggest that the process of hair cell maturation is not suppressed by the presence of aminoglycosides in the extracellular environment.

Steady state EP is not responsible for hearing loss in adult chickens following acoustic trauma.

The steady state DC endocochlear potential (EP) in young chicks shows a large decrease after acoustic overstimulation followed by a rapid recovery that parallels the recovery of threshold (Poje et al., Hear. Res. 82 (1995) 197-204). These results raise a question as to whether or not the EP could account for the hearing loss and make a significant contribution to the recovery of the threshold. In contrast to results in young chicks, we show that acoustic overstimulation, which causes extensive hair cell damage, does not cause a decrease in the steady state EP in adult chickens. However, there is a significant reduction in the negative EP seen during anoxia which persists even after 4 weeks of recovery. Thus, our results indicate that the steady state EP cannot account for the hearing loss observed in adult chickens.

Two-tone rate suppression boundaries of cochlear ganglion neurons in chickens following acoustic trauma.

The purpose of the present study was to examine the effects of acoustic trauma and hair cell loss and regeneration on the two-tone rate suppression (TTRS) boundaries of cochlear ganglion neurons in chickens. Chickens were exposed for 48 hours to a 525-Hz, 120-dB SPL tone which destroyed the hair cells and tectorial membrane in a crescent-shaped patch along the abneural side of the basilar papilla. Afterwards, TTRS boundaries were recorded from cochlear ganglion neurons at 0-1, 5, 14, and 28 days postexposure. Acoustic trauma reduced the percentage of neurons with TTRS boundaries below CF (TTRSb) (52.6% to 8.2%) and above CF (TTRSa) (88.4% to 46.6%). In addition, the exposure reduced TTRS boundary slopes, elevated best suppression threshold (BST), and increased the frequency separation between the tips of the TTRS boundaries and CF. All the TTRS measures started to recover by 5 days postexposure and by 14 days and 28 days postexposure, most measures had recovered to normal levels. However, the BST, TTRS slopes, and the frequency separation of TTRSb boundaries from CF were still slightly abnormal near the exposure frequency. In addition, the percentage of neurons with TTRS below CF was reduced significantly. The partial recovery of TTRS boundaries is presumably due to the regeneration of hair cells and the lower honeycomb layer of the tectorial membrane. The residual TTRS deficits observed 28 days postexposure were most closely associated with the missing upper fibrous layer of the tectorial membrane.

Tuning, spontaneous activity and tonotopic map in chicken cochlear ganglion neurons following sound-induced hair cell loss and regeneration.

Adult chickens were exposed for 48 h to a 525 Hz, 120 dB SPL tone that destroyed the hair cells and tectorial membrane in a crescent-shaped patch along the abneural edge of the basilar papilla. Single-unit recordings were obtained from cochlear ganglion neurons 0-1, 5, 14 and 28 days post-exposure to determine what effect the cochlear lesion had on neural discharge patterns and if the discharge patterns fully recovered. Immediately after exposure, the tuning curves were extremely broad and CF thresholds were elevated by 30-40 dB. In addition, the average spontaneous rate and percentage of neurons with interspike interval histograms with preferred intervals were greatly reduced. Tuning curves and spontaneous activity started to recover by 5 days post-exposure; however, some W-shaped tuning curves with two distinct tips and a hypersensitive tail were observed at this time. W-shaped tuning curves disappeared and spontaneous activity recovered to normal levels 14-28 days post-exposure. However, the CF thresholds of the most sensitive neurons were still slightly elevated, tuning curve slopes below CF were shallower than normal, and thresholds in the low-frequency tail of the tuning curves were often hypersensitive. These functional deficits were most closely associated with residual damage to the upper fibrous layer of the tectorial membrane. To determine if the cochlear frequency-place map was altered by the cochlear lesion, four physiologically characterized neurons were labeled with biocytin at 5 days post-exposure. The CFs of the labeled neurons were consistent with the normal frequency-place map (Chen et al. (1994) Hearing Research 81, 130-136) indicating that the tonotopic map was not altered.

Two-tone rate suppression boundaries of cochlear ganglion neurons in normal chickens.

The purpose of the present study was to provide a quantitative description of two-tone rate suppression boundaries in normal chickens. The boundaries were measured in 249 cochlear ganglion neurons using a tone 20 dB above threshold at the characteristic frequency (CF). The boundaries were present in 90.4% of neurons either on both sides or only one side of CF but more frequently above CF than below CF. The best suppression thresholds were positively correlated with and, on the average, 19-25 dB higher than CF thresholds. The boundary was farther from CF and shallower below CF than above CF. The boundary slope varied slightly with CF threshold and the tuning curve slope. These results are generally consistent with previous reports from mammals except that: (1) the boundary below CF did not follow and lie above the tuning curve flank; (2) the average best suppression threshold was slightly lower below CF than above CF; (3) the boundaries below and above CF were not particularly asymmetrical.

Effects of kanamycin ototoxicity and hair cell regeneration on the DC endocochlear potential in adult chickens.

High doses of aminoglycoside antibiotics cause massive damage to the avian basilar papilla. The resulting functional loss could conceivably arise from the reduction in the DC endocochlear potential (EP) due to impairment of the tegmentum vasculosum (TV) or to shunting of current through the damaged sensory epithelium. To test this hypothesis, the EP was measured in adult chickens after destroying hair cells in the basal half of the cochlea with a high dose (400 mg/kg per day for 10 days) of kanamycin (KM). KM treatment caused an increase in the steady-state EP from +18.1 to +23.3 mV and a decrease in the magnitude of the negative EP from -42.0 to -19.2 mV. The EP showed almost no change between 1 and 2 days and 1 week post-KM treatment. After 4 weeks of recovery, most hair cells had regenerated; however, the steady-state EP was still elevated by 13% and the negative EP was depressed by 37%. These results suggest that functional loss as shown by the large reduction in cochlear microphonic (CM) and the elevated thresholds of compound action potential (CAP) following KM treatment is not due to a reduction in the EP but may arise from functional deficits in the hair cells and/or the auditory nerve.