Murray B. Sachs - US grants

The focus of this Research and Training Center in Hearing and Balance is the study of labyrinthine from the biophysics of hair cell mechanisms to the rehabilitation of patients with unilateral hearing loss. The research we propose is focused on three closely related areas: mechanisms of hair cell damage; testing and rehabilitation of patients with unilateral vestibular lesions; and signal processing in the brainstem auditory system. One group of three projects focuses on in vitro and in vivo studies of these mechanisms of action of pharmacological and environmental ototoxins and on ways to mitigate these effects. A group of four projects attempts to devise better ways to evaluate otolith function, to learn more about vestibula-ocular adaptation with implications for the design of physical therapies, to examine effects of anti-motion sickness medications, and to test the efficacy of physical therapy on improvement of vestibular function in patients with unilateral lesions. A final group of four projects focuses on the role of on and of other sensory inputs on signal processing in the cochlear nucleus. Our proposed training program will integrate training in hearing and balance and will provide for strong interactions between basic science and clinical trainees and faculty. This program takes advantage of the Hopkins strength in basic and clinical science. Among a number of novel features that build on an already established training program are the development of a clinical rotation for basic science trainees, an integrated research and clinical residency for selected clinician scientists, a neuro-otology postdoctoral program for otolaryngologists, neurologists, audiologists and physical therapists, and a sabbatical plan to bring scientists and clinicians to our Center from institutions with inadequate research environments. We propose a series of continuing education symposia in hearing and balance for health professionals that will address important clinical issues with a firm grounding in basic research. We will offer a continuing studies course that will make current information on hearing and balance function and disorders accessible to the local professional and lay communities. Finally, we propose to develop a broad information dissemination program to reach health professionals, the lay public, opinion leaders and patients. This program will take advantage of the extensive Hopkins Public Affairs machinery.

This proposal requests fund for renovation of laboratory facilities in Krieger Hall, a primary research laboratory building. The renovation and remodeling will provide the resources to locate more members of the Department of Biomedical Engineering in proximity to other engineering departments with a greater opportunity for joint research in areas including biomedical sensors, biomaterial and biomedical imaging systems. Funds will also be used for renovating an interdisciplinary, interdepartmental microfabrication facility for researchers in the G.W.C. Whiting School of Engineering. The development of such a facility will require major renovation or replacement of an existing clean room to add exhaust systems for safe use of chemicals and gases needed in microfabrication, and an improved air filtration systems to reduce particle counts. The facility will be used by faculty throughout the engineering school including faculty in biomedical, electrical, chemical engineering, and materials science in the conduct of sponsored research. Ongoing projects in diverse areas such as microfabricated biomedical sensors, compound semiconductors lasers, microwave devices, analog integrated circuits, electoractive polymers, porous silicon studies, barrier properties of polyamide layers, would benefit from this facility. Use of this common facility by the participants and their trainees (postdocs, graduate and undergraduate students) will improve the interdisciplinary interactions in this technical area.

The long-term goal of the proposed work is to improve our understanding of the neural representation of speech in the presence of sensorineural hearing loss. Single neuron recordings will be made in cats exposed to intense noise, which produces a hearing loss comparable to moderate high frequency loss (greater than or equal to 1 kHz). The first aim is designed to test and further develop a way of compensating for the loss of sharp cochlear tuning and nonlinear suppression in damaged cochleas. The aim is to develop a method of specifying the optimum spectral shape for presenting a particular speech sound to an ear with a particular hearing loss, where optimum means designed to produce patterns of auditory nerve activity that are as normal as possible. The second aim will characterize neural responses to running speech, instead of the isolated phonemes that are usually used in auditory experiments. The representation of sentence-level speech will be characterized in both the spectral and temporal domains, for both normal and damaged ears. The compensation methods developed in the first aim will be tested using these stimuli. The effects of background noise will also be examined. In the third aim, an accurate computational model of auditory nerve activity in a damaged ear will be developed. Development and testing of the model will be closely coordinated with the experimental studies of the first two aims. The goal is to produce a model which is accurate enough to be used as a test bed for developing hearing-aid signal- processing. The final aim will study how cats with a hearing loss discriminate variants of the vowel /epsilon/ with different second formant frequencies. These behavioral experiments are designed to differentiate between two models of information representation in the auditory nerve, the so-called rate-place, and temporal-place models. The experiments take advantage of the fact that cats with a moderate hearing loss do not have rate-place information which would allow them to discriminate these vowels. This aim will provide evidence, for the first time, on the relative importance of the two information representation codes in the auditory nerve and will be important in interpreting the results of the experiments in the other three aims.