Absolute and Intensity Difference Thresholds in the Guinea Pig Before and After Aminoglycoside-Treatment and Cochlear Injury.

The acoustic acuity of the guinea pig (Cavia porcellus), heretofore believed to be an intractable behavioral subject, was investigated in this study using operant conditioning and the methods of positive reinforcement. On the basis of data from 12 subjects, guinea pigs were found to be reliable reporters of auditory events. Subjects were sensitive to pure-tone stimuli from 0.125 to 45.0 kHz, with optimum acuity between 4.0 and 16.0 kHz. After stable absolute thresholds were determined, 7 subjects were treated with kanamycin (KM), an aminoglycosidic antibiotic, at either 200 or 100 mg/kg body weight subcutaneously until an absolute threshold shift of 40-50 dB at 8.0-16.0 kHz was observed. Neither dosage level nor total amount of drug administered reliably predicted the final extent of the receptor cell destruction and the permanent hearing loss. A 40-60 dB permanent absolute threshold shift was consistently associated with basilar membrane areas with complete outer hair cell (OHC) loss and good inner hair cell (IHC) retention. Intermediate gradations of OHC loss led to absolute threshold shifts less than 40 dB. In a separate experiment, two subjects treated with 100 mg/kg/day of amikacin, a semisynthetic derivative of KM, showed a similar pattern of permanent threshold shift and receptor cell loss as the KM-treated subjects, indicating that KM and amikacin act similarly as ototoxic agents in the guinea pig cochlea. Data from both the amikacin- and the KM-treated subjects suggested that OHC loss leads to decreased absolute sensitivity of 40-60 dB. In the final experiment, intensity difference and absolute thresholds were determined in the remaining 3 subjects. Intensity difference limens (IdLs) were determined for each subject at 2 or more frequencies, and 2 or more sensation levels (SL). IdLs ranged from 3.2 dB at 70 dB SL, to 6.6 dB at 20 dB SL, and compared favorably with IdLs of other non-human creatures. The effect of absolute intensity, such that IdLs were smaller at higher sound pressure levels (SPLs), was a feature of both human and non-human IdLs reported in the literature. Two subjects in which baseline IdLs had been established were subsequently treated with KM until an absolute threshold shift of 30-50 dB was noted at the highest frequency at which IdLs were determined. Following a moderate absolute threshold shift, IdLs were unchanged when assessed at a constant SPL; when measured at a constant SL, they improved. The finding that the IdLs are smaller after cochlear trauma when assessed at a constant SL was precisely the trend reported in the early human literature; this finding formed the basis of the Short Increment Sensitivity Index (SISI) test, used to diagnose cochlear pathology. The test was later described as an unreliable indicator of trauma when conducted at high SPLs, a finding which the results of the present study fully support. Since, in concurrence with the 35-55 dB absolute threshold shift reported by the two guinea pigs of this study, the OHCs were partially or totally destroyed while the IHCs were mostly retained, it was concluded that the OHCs, necessary for normal absolute sensitivity, are not needed for normal intensity discrimination. Finally, data from a variety of studies are reviewed which in concert suggest that loudness encoding, and perhaps loudness perception, are normal at high sound pressure levels in the cochlea with moderate sensorineural damage.PhDPsychobiologyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/157974/1/8025748.pd