Douglas H. Keefe, Ph.D. - US grants

DESCRIPTION (From applicant's proposal): The main theme of the proposed research is to increase our knowledge of the human middle ear and cochlea based upon the use of acoustic response testing in the ear canal. Such tests are inherently noninvasive so that it is hoped that the knowledge gained on basic mechanisms in hearing will have significance for clinical utilization. The first aim is to examine new forms of otoacoustic emissions (OAE), which will provide a clearer understanding of mechanical processes on the basilar membrane. Time-frequency representations of OAE transients will delineate the fine structure of the tonotopically organized cochlear dynamics, which is otherwise partially obscured by conventional waveform or spectral representations. The second aim is to assess middle-ear and cochlear mechanisms in an integrated manner using a power-transfer approach. Such an approach will combine aspects of wideband tympanometry, otoreflectance and OAE measurements to interpret power flow from the ear canal through the middle ear to the cochlea, and back. The third aim will apply these new types and representations of OAEs and the power-transfer approach in large-scale studies of normal ears, and ears with middle-ear and cochlear impairments. The goal is to improve techniques to predict conductive, cochlear and mixed hearing losses, and to better understand how acoustic response variables can be combined, for example, across frequency or static pressure in the ear canal, in order to understand the underlying cochlear and middle-ear mechanics and coupling in normal and impaired ears. The results of the proposed experiments will provide useful data for theoretical modeling of the auditory periphery, and could significantly improve our ability to identify persons with conductive or cochlear hearing loss.

DESCRIPTION (provided by applicant): The primary goal of this application is to use a combination of acoustic and behavioral responses to test theories of auditory processing at the mechanical and behavioral levels. A subordinate goal is to relate acoustic responses measured non-invasively in the ear canal to cochlear and middle ear function. The first aim studies the relationships between middle ear and cochlear mechanics using a combination of experimental and theoretical approaches. Measurements of stimulus-frequency otoacoustic emission (SFOAE) and otoreflectance measurements will be used to predict hearing loss, an improved test of acoustic reflex function will be used to study middle-ear noise sources and no linearity, and time-domain models of middle-ear and cochlear energy transmission will be developed and evaluated based on experimental measurements performed in this application or reported in the literature. The second aim studies the effects of cochlear no linearity on spectral processing using SFOAE stimulus conditions similar to those used in behavioral experiments on simultaneous and non-simultaneous masking and suppression. Specifically, the experiments will address the extent to which SFOAE measurements of peripheral mechanics are able to noninvasive assess the strength of the medial olive-cochlear (MOC) efferent system on outer hair cell function, assess the level dependence of SFOAE fine structure, and account for the performance of normal-hearing listeners and listeners with sensor neural hearing loss in detecting tones in broadband and notched noise. The third aim studies the effects of cochlear no linearity on temporal processing using SFOAE stimulus conditions similar to those used in behavioral experiments on overshoot and amplitude modulation (AM). These experiments will assess the shifts in SFOAEs produced by activation of the MOC system in response to sounds with AM, and will test the extent to which SFOAE measurements can account for measurements of behavioral overshoot in normal listeners and subjects with auditory neuropathy. The results of the proposed experiments will provide useful data and modeling to improve our understanding of the auditory periphery in humans, and may improve our ability to diagnose the magnitude of hearing loss and improve our understanding of the impact of hearing loss on spectral and temporal resolution.

DESCRIPTION: Wideband Clinical Diagnosis and Monitoring of Middle-Ear and Cochlear Function A wideband (WB) acoustic test battery has the potential to improve hearing screening and diagnosis of middle-ear and cochlear dysfunction across the age range. The WB test battery addresses current limitations in newborn hearing screening (NHS) and diagnostic programs, and may improve adult programs to identify ototoxic hearing loss and diagnose middle-ear disease in patients receiving middle-ear surgery. The tests measure acoustic responses to sounds presented in the ear canal. The acoustic immittance tests in the battery to assess middle-ear function are an acoustic transfer function (ATF) test and an acoustic- reflex threshold (ART) test. The ATF test provides admittance, absorbance and reflectance responses over frequencies important for speech perception (0.2-8 kHz), and is performed either at ambient pressure or as a WB tympanogram. The ambient-pressure ATF may have advantages for testing newborns in the first months of life, whereas the WB tympanogram may have advantages for testing older infants and adults. The WB ART test objectively measures an infant's threshold and may improve the accuracy of newborn hearing screen programs to identify sensorineural hearing loss (SNHL) and conductive hearing loss (CHL). The WB click-evoked (CE) otoacoustic emission (OAE) test in the battery assesses cochlear function using an extended bandwidth relative to clinical CEOAE tests. Aim 1 assesses whether adding a WB test battery to the initial and follow-up NHS exams improves the accuracy of detecting SNHL and CHL. More accurate diagnoses would improve follow-up clinical care provided to infants with hearing disorders. Aim 2 evaluates whether middle-ear problems detected by the WB test battery in NHS can predict continued middle-ear dysfunction in the first year of life. No clinical guidelines exist on how to manage these infants, due to a lack of evidence regarding the incidence, duration and importance of CHL associated with NHS referrals. Aim 3 evaluates whether WB immittance tests can detect CHL in infants with cranial-facial anomalies and development delays. An objective physiological test to accurately predict CHL is urgently needed because audiometry in this group is affected by cognitive status. In Aim 4 with adults, the extended bandwidth of the CEOAE at least out to 10 kHz is well suited to detect early hearing loss in cystic fibrosis patients receiving ototoxic medications. Such a test would serve as a complement in medical clinics to a more extensive assessment using behavioral audiometry. Aim 5 would evaluate whether the WB test battery improves the differential diagnoses of otoscleroris and ossicular discontinuity in adults receiving middle-ear surgery. These disorders are difficult to classify using current diagnostic tests, and an accurate physiological test would improve clinical management and post-surgical monitoring of middle-ear function in patients. Public Health Relevance: Wideband Clinical Diagnosis and Monitoring of Middle-Ear and Cochlear Function A wideband test battery has translational potential to more accurately identify middle-ear and cochlear conditions in patients across the age range. The proposed research evaluates whether the use of this test battery improves the quality of newborn hearing screening programs to identify infants with hearing loss. The research also evaluates whether the test battery improves the accuracy of diagnosing middle-ear disease and of identifying hearing loss in adult patients who receive medications that may affect their hearing.

? DESCRIPTION (provided by applicant): This application requests support for three postdoctoral positions in a multidisciplinary research training program in the area of human communication and its disorders at Boys Town National Research Hospital (BTNRH). The training program at BTNRH, currently in its 34th year, has provided postdoctoral training to a substantial number of highly qualified scientists who are presently working in the field of communication disorders. The purpose of the program is to fulfill two basic training needs: 1) advanced research training for applicants who are recent graduates of speech and hearing, communication sciences or language-related doctoral programs, and 2) training for applicants with a received doctorate in a related field of science, technology, engineering or mathematics who would benefit from additional research experience in a collaborative, research-intensive environment. The training program consists primarily of direct participation by trainees in behavioral and clinical translational research under the sponsorship of one or more experienced, independent scientists serving on the program faculty. Research at BTNRH is conducted in a wide range of disciplines and laboratories from clinical audiology to language development, with the focus on questions concerning the mechanisms underlying human communication and its disorders. The unique advantages of the BTNRH research environment for the training program include: 1) a faculty consisting of 13 behavioral, clinical and translational clinical scientists who serve as mentors; 2) a critical mass of research trainees, funded by a variety of mechanisms, including T32, F32, COBRE and R01 grants; 3) a clinical staff with access to a large and varied pediatric and adult patient population; 4) modern, well-equipped laboratories and diagnostic clinics; 5) a stimulating mix of areas of research across individual research laboratories; 6) access to a new auditory- visual core facility; and 7) conditions that foster collaborative, multi-disciplinary research. Trainees are selected from PhD's, DSc's, and MD's in areas relevant to ongoing research programs at BTNRH on the basis of their research capabilities and the likelihood of their interacting productively with training faculty. Particular attention is paid to identifying and inviting applications to the program from under- represented minority candidates and candidates with a disability. Every effort is made to enhance diversity in the postdoctoral training program and eventually in the group of scientists performing research related to the mission of the NIDCD.

The Technical Core will deliver laboratory computing and engineering support to the projects of the junior investigators in the Center for Perception and Communication in Children through a staff skilled in research programming and signal processing. The proposed projects in children with normal hearing and children with hearing loss will address theories and experiments on hearing, speech perception, language development, auditory-visual signal processing, and interactions of vestibular and visual function. The programming staff of the Technical Core will support the proposed experiments in procedures for stimulus presentation and recording of acoustical, visual and vestibular-related signals, and will assist the investigators in data analyses. The Technical Core will develop an Auditory-Visual Core Facility for communications research using human subjects, which will enable precise experimental control over spatial and temporal variability in auditory and visual stimuli. The staff will include architectural acousticians to consult with junior investigators on the design and interpretation of experiments requiring the systematic variation and/or measurement of room acoustical effects. This multi-user auditory-visual room facility will have unique capabilities for addressing theories of communications research in children. The Technical Core will serve as an innovative resource of skilled programmers and engineers, and will support investigators' research in its Auditory-Visual Core Facility.

PROJECT SUMMARY/ABSTRACT This project develops and evaluates procedures to estimate the ear-canal sound field near the tympanic membrane (TM). The underlying framework of these procedures is to model the ear canal as an acoustic waveguide. Spatial variation in the cross-sectional area of the ear canal is described acoustically by quantifying forward and reverse sound waves traveling between a probe inserted into the ear canal and a location near the TM. Describing the sound field near the TM in terms of sound pressure and its reflected and transmitted components more accurately quantifies the acoustical high frequency (HF) input to the middle ear. Such a description improves HF calibration of the stimulus near the TM for physiological tests such as otoacoustic emission and auditory brainstem responses, and HF behavioral tests such as extended audiometry and tests of spatial processing of sound. The specification also improves the ability to describe forward and reverse otoacoustic emission responses at HFs, which non-invasively encode information on outer-hair cell function within the cochlea. The project outcomes will benefit acoustic diagnostic tests of middle-ear and cochlear function. The goals of Aim 1 are to: (i) implement and evaluate a causal, time-domain measurement at the probe tip of the acoustic reflection function (RF) of the ear, such that reflectance is the Fourier transform of the RF, (ii) use the RF to calculate area-distance functions of the ear canal between the probe tip and TM, and (iii) use RF and area data to estimate the sound field near the TM (i.e., to within 3.6 mm). Current frequency- domain tests to measure reflectance are not constrained to obey causality, which limits their accuracy in clinical applications, especially at frequencies above 8 kHz. Causality requires that sound cannot be reflected prior to its incidence. The RF of the ear is a key response for subsequent area-distance calculations within the ear canal. RF data will be acquired in Aim 1 experiments in tubing systems with varying areas, molds of ear canals and an artificial ear simulator (IEC711 coupler). Present approaches to describe the area-distance function in the ear canal largely use the Webster, or plane-wave, horn equation, which is of insufficient accuracy for the area variations in the ear canal. This project will measure area-distance functions using a novel spherical-wave horn model that controls for changes in the taper of the ear canal. These area-distance algorithms include a novel time-domain description of losses at the ear-canal walls. The goals of Aim 2 are to: (i) acquire RF data in groups of 5-year-old children and adults with normal hearing, (ii) calculate area-distance functions in their canal, (iii) use a digital scanner to measure the ear-canal geometry, (iv) compare acoustic and scanned measurements of the area-distance function, (v) estimate the sound field pressure, and transmission and reflection of sound, near the TM, and (vi) test for maturational differences in ear-canal and middle-ear function in children relative to adults. The approach makes maximal use of the acoustic data provided in a probe measurement within the ear canal.