Manuel Don - US grants

DESCRIPTION: (Adapted from the Applicant's Abstract.) The major long-term objective of this proposal is to combine three ABR techniques that will help to delineate objectively and quantitatively the relationship between ABRs and peripheral hearing loss. This combination of techniques will allow evaluation of ABRs initiated from specific regions of the cochlea, specify error rates of threshold measures, reduce the variability of response parameter measurements, and optimize clinical test time. The three ABR techniques to be combined are a masking one for measuring the cochlear-place specific ABRs, a statistical one for objectively defining ABR threshold based on response properties rather than visual interpretation, and a weighted averaging one based on Bayesian principles using estimates of the background noise. A second long-term objective is to find an independent ABR threshold measure that can be used simultaneously with the above combinations to improve detection rates without compromising false-positive error rates. The third long-term objective is to develop these techniques to run on a micro-computer-based system to facilitate widespread clinical use. Six specific aims of the proposed research focus on evaluating normal and hearing-impaired patients with the combination of techniques, delineating the effects of stimulus parameters, evaluating methods to minimize the noise in the averages, and evaluating the joint use of other independent objective ABR measures to improve detection. The proposed work may fill critical, unmet needs in the current clinical use of ABRs for diagnostic information by providing a better understanding of the complex relationship between perceptual and electrophysiological measures in hearing-impaired patients, maximizing the averaging efficiency, and developing a truly objective, quantitative and consistent ABR method for estimating the audiogram and measuring response parameters.

DESCRIPTION: (Adapted from the Investigator's Abstract) The project's long-term goal is to understand the effects of otologic pathology on mechanisms underlying human cochlear and brainstem processes. It proposes a mechanism-based approach that will provide (1) critical neuro-patho-physiological information, and (2) a scientific framework for early diagnoses of difficult-to-identify otologic diseases. In this approach, it uses newly-developed non-invasive measures of the auditory brainstem response (ABR) to investigate known and hypothesized pathological changes in the mechanisms underlying specific processes in the peripheral auditory system caused by small acoustic tumors and Meniere's disease. The specific aims are (1) to demonstrate that small (<1 cm) acoustic tumors alter the synchrony and/or amount of neural output to an extent greater than that predicted by audiometric thresholds, and (2) to determine if patients diagnosed with Meniere's disease have abnormal cochlear temporal-related measures consistent with the presence of cochlear hydrops. In addition, a comparative analysis of the results of these studies will determine whether the proposed measures can distinguish between small acoustic tumors and early Meniere's disease. The significance of the proposed work is that it will (1) provide new insight into the effects of otologic pathology on the theoretical and basic scientific mechanisms underlying the human peripheral auditory system, (2) demonstrate that non-invasive physiologic measures guided by a mechanism-based approach can lead to sensitive diagnoses for small acoustic tumors and early Meniere's disease with good specificity, (3) fill the need for non-invasive measures of peripheral auditory system functionality in humans as new therapeutic measures to improve, prevent destruction of, or possibly restore cochlear function are developed, and (4) test the predictive power of currently emerging models of cochlear and brainstem function across the domains of cochlear physiology, neurophysiology, electrophysiology, and pathology.