Forward Acoustic Masking Enhances The Auditory Brainstem Response In Rats With Tinnitus

BACKGROUND:Tinnitus is a common hearing disorder. According to statistics, about4.4%-15.1%of people have experienced tinnitus. The lack of objective tinnitus measurement program is one of the constraints to tinnitus research. The principal method for the tinnitus patient is self-assessment measurement, and one for animal models of tinnitus is the behavioral method. For the treatment of tinnitus patient and the treatment’s evaluation, and for research in animal models of tinnitus, an objective measurement method is required. However, there is currently no low-cost and simple objective measurement method available. In the present study, the auditory brainstem response (ABR) was found to be enhanced by forward acoustic masking in tinnitus animal model. This phenomenon is expected to be a new objective tinnitus measurement method.METHODS:In the present study, sodium salicylate (NaSal,300mg/kg, i.p.) was systemically administered in Wistar rats to induce tinnitus. Specially designed auditory stimuli were presented to rats. The ABRs were recorded in closed acoustic field under two conditions:(1) the forward masker and the probe were presented to both ears (diotic paradigm);(2) the forward masker was presented to one ear and the probe to the other ear (dichotic paradigm). The ABRs were analyzed to determine the status and activities of the brain in rats. The gap prepulse inhibition of acoustic startle (GPIAS) as a tinnitus behavioral index was recorded for supporting the ABR data.RESULTS:Forward acoustic masking suppressed the ABR to the probe tone before NaSal treatment under the diotic condition, which is consistent with the notion that the auditory response to an acoustic stimulus will usually be suppressed, or masked, by a preceding sound. After treatment with a high dose of NaSal in rats, however, forward acoustic masking surprisingly enhanced the ABR to the probe tone at the high frequencies (16,24and32kHz). Further data analysis indicated that forward masking did not increase the peak-to-peak amplitude of ABR wave I produced by the auditory nerve, but significantly increased ABR waves II and IV produced by the central auditory system at high frequencies in NaSal-treated rats. In the dichotic condition, the forward masking failed to enhance the ABR in NaSal-treated rats. In addition, the GPIAS was reduced at the frequencies at which the forward masker enhanced the ABR in the diotic condition in NaSal treated rats. Vigabatrin, which is a GABA transaminase inhibitor and has been shown to suppress NaSal-induced tinnitus in animals, prevented forward masking from enhancing the ABR in NaSal-treated rats. The enhancing effect of forward masking on the ABR could be mimicked by presenting a pure background tone (artificial tinnitus). These results demonstrate that the observed enhancement of ABRs caused by forward acoustic masking originates in the central auditory pathway ipsilateral to the stimulated ear and suggest a possible link of the enhancement to tinnitus.DISCUSSION:A working hypothesis was proposed in the present study to explain how forward acoustic masking can enhance the ABR in rats treated with a high dose of NaSal. Briefly, without a forward masker, NaSal-induced tinnitus will exert an "internal masking" effect on the probe tone due to the increased central neural noise to keep the ABR in a suppressed state. With a forward masker, however, tinnitus will be masked out by the masker and this masking effect will persist beyond offset of the masker and then diminish (residual inhibition). The residual inhibition is assumed to persist much longer than the forward masking. Thus, the ABR to the probe tone will rebound, or will be enhanced from the suppressed state following the forward masker. In other words, forward acoustic masking can transiently silence NaSal-induced tinnitus for the otherwise suppressed ABR to rebound.If the findings in the present study can be verified and confirmed, these findings may serve as a new objective method for subjective tinnitus. This method is expected to be quick, economic and objective. The method is expected to have frequency sensitivity, so it could be used to measure the frequency of tinnitus. The method is also expected to have intensity sensitivity, so it could be used to measure the subjective loudness of tinnitus. Because the ABR directly reflects the activities of the auditory brainstem, the method is expected to avoid the other uncertainty (such as movement or cognition disorders caused by drugs, aging, etc.). Moreover, using the ABR as the method of tinnitus measurement, the time and cost used for training animals can be saved, and simultaneously measuring tinnitus in multiple animals is possible. These findings may provide a convenient tinnitus measure in animals which is much-needed in tinnitus research, and raises a new possibility to economically screen tinnitus drugs on a large scale.