PP1309 - Complex Auditory Brainstem Response Measures Using Tones-in-Noise

Abstract: Auditory brainstem response (ABR) correlates are typically used to assess auditory neural activity in response to simple stimuli, such as clicks or tone bursts, that may not tax the auditory system. In comparison, complex auditory brainstem responses (cABR) can be used to assess higher-order auditory abilities by utilizing more complex signals to evoke responses, like tones-in-noise stimuli. The tones-in-noise cABR has been suggested as a potential objective measure of various cochlear lesions that may go undetected by threshold measures, such as the selective loss of inner hair cells or their synaptic connections, and may better indicate functional hearing-in-noise ability.

Summary:

The auditory brainstem response (ABR) is a widely used clinical measure for objectively assessing pathologies affecting the brainstem pathway and to estimate hearing sensitivity. Short, simple stimuli, such as clicks and tone bursts, are typically used for ABR evaluation. Yet, several pre-clinical physiological studies measuring ABR outcomes using simple stimuli have shown little to no change in thresholds following selective loss of IHCs or synaptopathy. In contrast, such cochlear lesions have been shown to reduce the amplitude of the ABR wave-I, even in the absence of elevated thresholds. These findings suggest that wave-I of the ABR could be used to detect IHC loss and damaged afferent connections. However, wave-I amplitudes are known to vary greatly in human patients, limiting their use as a physiological biomarker of IHC lesions in patients with minimal hearing loss or auditory complaints without threshold elevation. Conversely, ABR wave-V has been found to be a robust and repeatable measure in humans that allows for measures within background noise. Wave-V arises from the lateral lemniscus and inferior colliculus, and due to central gain compensation, wave-V amplitudes are often not reduced by selective damage or loss of IHCs. However, increasing levels of background noise result in a shift in wave-V latency and these latency shifts are believed to correlate with perceptual measures of fine-temporal coding. Although not often utilized in clinical settings, the ABR can also be recorded in response to complex stimuli (cABR), including noise, speech, and music. Additionally, the cABR and may allow for more precise assessments of temporal and frequency representations relative to traditional ABR threshold measures. For the current investigation, we evaluated the relationship among suprathreshold ABR wave-I amplitudes using tone-bursts and cABR wave-IV latencies using tones-in-noise before and after carboplatin-induced selective IHC loss in the chinchilla. We hypothesized that IHC loss would reduce ABR wave-I amplitudes and increase cABR wave-IV latencies.

Design:

Young-adult chinchillas were used to evaluate effects of selective IHC loss on suprathreshold cABR measures before and after carboplatin-treatment. Distortion product otoacoustic emissions (DPOAE) and ABR thresholds were obtained to assess the status of cochlear nonlinearity and as a measure of overall hearing sensitivity. Suprathreshold ABR correlates were measured bilaterally at 90, 80, and 70 dB SPL with 1, 2, 4, 8, and 12 kHz tone bursts in quiet and tones embedded in broadband noise of varying intensities with signal-to-noise ratios (SNR) ranging from +10 to -5 dB SPL. Following baseline measures, animals were treated with a single dose of 75 mg/kg of the anticancer drug carboplatin, a dose known to reliably produce 50 – 80% IHC loss with outer hair cells (OHC) remaining intact. Post-carboplatin assessments were performed three weeks following treatment to allow for recovery time. 

Results &

Conclusions:

As expected, carboplatin-treatment had no significant effect on ABR thresholds and DPAEs, suggesting survival and function of OHCs. ABR wave-I amplitudes were substantially reduced, even in the absence of elevated thresholds. Wave-I/IV interpeak latency changes of the cABR were minimal and may reveal central gain and compensation occurring prior to wave-V.