Bertrand Delgutte, Ph.D. - US grants

This proposal requests funds for a state-of-the-art, computer- control system for auditory physiological experiments. The proposed system consists of a Masscomp computer system that is ideally suited for fast input/output of analog data and a variety of programmable electronic devices that control computer-generated acoustic stimuli and process acoustic, electric, and mechanical signals recorded from the ear and the brain of experimental animals. This system will serve a tightly-knit community of investigators who work on all stages of the auditory system from the external ear to central neural pathways of the brainstem. It is a prototype for a new generation of data acquisition systems destined to replace 15-year old systems based on PDP-8E computers that have become obsolete and overextended. The new system will be built around an existing, high-quality sound-proof chamber that has been waiting to be fully instrumented. New trends in auditory physiology create a demand for a facility with capabilities beyond those presently available. Some of these new features are computer generation of acoustic and electric stimuli, multiple, precisely- synchronized stimulus and response channels, flexible processing of discrete event data such as neural discharges, and sufficient computational power to allow online test of predictions from mathematical models with data from physiological experiments. The proposed system will enable investigators to have all of these capabilities and bring physiological studies to a new level of flexibility an efficiency.

Speech is by far the most important class of acoustic stimuli for human listeners. While the coding of speech in the auditory nerve is relatively well understood, and some information is available for cochlear-nucleus neurons, very little is known about the responses of more central neurons to speech stimuli. We propose to study the responses of single neurons in the inferior colliculus (IC) of anesthetized cats to a wide variety of speech and speech-like sounds encompassing the acoustic characteristics used in English and other languages. One series of experiments will examine how the formant frequencies and fundamental frequency of vowels are coded in the discharge patterns of IC neurons, using synthetic stimuli in which these parameters ar systematically varied over a range appropriate for both male and female voices. These responses will be compared with those for sine-wave speech and amplitude-modulated tones in order to determine whether responses to vowels can be predicted from responses to simpler stimuli. Another series of experiments will study the responses to consonants differing in voicing, place, and manner of articulation. In particular, we will examine how the responses to consonants are affected by the preceding context. These responses will be compared with those to pairs of tones presented in succession in order to determine whether mechanisms such as adaptation, facilitation and long-lasting inhibition enhance the response to particular speech features. This research addresses fundamental issues in speech perception such as the neural basis for categorical perception, and the perceptual invariance of speech sounds in the face of context-dependence in their acoustic characteristics. By providing direct knowledge of the neural coding of speech in the brainstem, this research may also help design speech processors for auditory (cochlear and brainstem) implants that would be more effective by providing information appropriately coded for specific parts of the central auditory system. In combination with research on spatial hearing, this work may also lead to a better understanding of why hearing-impaired and elderly listeners have much greater difficulties understanding speech among competing sounds than do normal listeners, and may help develop new kinds of hearing aids that would perform better in noisy environments.

DESCRIPTION (provided by applicant): Most speech conversations occur in the presence of competing sounds and acoustic reflections from room surfaces. Hearing-impaired people often complain of difficulties understanding speech in such complex acoustic environments even if they do well in quiet. Here we propose neurophysiological and computational studies that address fundamental questions about two aspects of listening in complex environments: (1) How the auditory system compensates for the degradation in the acoustic signal caused by reverberation;(2) How the auditory system extracts the pitch of harmonic complex tones, one of the main cues used by listeners to segregate simultaneous sound sources. We will record from single units in the auditory nerve (AN), ventral cochlear nucleus (VCN) and inferior colliculus (IC) in response to complex sounds that incorporate some features of complex acoustic environments, and develop computational models that predict these responses. Specific Aim 1 is to test the hypothesis that the auditory system contains neural mechanisms that allow it to preserve good directional and temporal sensitivity in reverberation. We will measure the directional and temporal envelope sensitivity of IC neurons in simulated room environments, compare these responses with predictions of existing models of binaural processing, and develop new models incorporating reverberation compensation mechanisms. Aim 2 is to test the hypothesis that the cochlear traveling wave creates robust spatio-temporal cues to the pitch of complex tones that can be extracted by a neural mechanism sensitive to the relative timing of spike discharges from AN fibers tuned to slightly different frequencies. We will test the availability and robustness of these spatio-temporal pitch cues in the AN, then examine whether these cues can be extracted by neurons in the VCN known to be sensitive to monaural phase. This research addresses fundamental issues in auditory theory such as the neural mechanisms for pitch processing, the mechanisms for echo suppression in reverberation, and mechanisms of sound source segregation. It may lead to a better understanding of why hearing-impaired and elderly listeners have greater difficulties understanding speech in the presence of reverberation and competing sounds than do normal listeners, and may help develop new kinds of hearing aids and auditory (cochlear and brainstem) implants that perform better in challenging environments.

Binaural hearing is essential for accurate sound localization and for hearing out sounds of interest among competing sound sources, and these binaural advantages are an important motivating factor for the increasing number of bilateral cochlear implants. In this application, investigators from three laboratories at the Massachusetts Eye and Ear Infirmary, MIT, and Boston University join together to propose closely- integrated psychophysical, neural and modeling studies that seek to identify the best stimulus configurations for effectively encoding binaural information in bilateral implants. The primary focus is on interaural time differences (ITD) because ITD is a dominant cue for sound localization, and because binaural advantages in detection depend on ITD. The psychophysical experiments will be conducted in human patients implanted bilaterally with Clarion devices. The neural experiments will be conducted in deafened, anesthetized cats implanted bilaterally with intracochlear electrode arrays. Single and multi-unit recordings will be made from the inferior colliculus (IC), for which a great deal of information is available on binaural properties of neurons. In order to explicitly and quantitatively test our understanding of the empirical results, we will also use models of binaural processing to predict both IC responses and psychophysical abilities from ch_[unreadable]cr,inticm_ nf anditorv nerve activity in responm to electric stimulation. The s_cific aims are to (1) letermine the relative effectiveness of temporal envelope and fine structure for ITD coding in electric hearing, (2) determine how 1TD sensitivity depends on interaural disparities in cochlear locations of the stimulating electrodes, (3) determine whether there is a binaural advantage for signal detection in noise with bilateral stimulation. An important goal of these experiments will be to test a novel processing strategy that seeks to improve the representation of the stimulus waveform in temporal discharge patterns of auditory neurons by using an ongoing, high-rate, desynchronizing pulse train as the carrier waveform. Overall, these studies will provide basic knowledge about the stimulus parameters that influence binaural interactions in electric hearing and are likely to lead to new processor designs specifically adapted to bilateral cochlear implants.

DESCRIPTION (provided by applicant): Bilateral cochlear implantation provides benefits over unilateral implantation for sound localization and speech reception in noise, yet binaural performance of bilateral cochlear implant (CI) users is still well below normal, especially in task involving interaural time differences (ITD), and especially in pre-lingually deaf subjects. The present collaboration between neurophysiologists and psychophysicists aims at gaining a basic understanding of the stimulus, neural, perceptual and developmental factors that influence ITD sensitivity with bilateral CIs in order to devise innovative stimulation and rehabilitation strateges that improve binaural performance. Psychophysical experiments in bilaterally-implanted human subjects will be conducted in parallel with single-unit recordings from the auditory midbrain in a novel, awake rabbit model of bilateral CIs that allows neural recordings over several months. Specific Aim 1 is to investigate whether the abnormalities in neural ITD sensitivity previously observed in neonatally deaf animals can be reversed by appropriate chronic electric stimulation through bilateral CIs. We will compare neural ITD sensitivity in neonatally-deafened rabbits that receive various types of chronic electric stimulation from an early age with the sensitivity in dea rabbits that receive minimal stimulation. Some of the rabbits will receive stimulation with an experimental strategy that was specifically designed to deliver ITD information effectively with bilateral CIs, and some rabbits will only receive unilateral stimulation as occurs during the perio of unilateral deafness between the two cochlear implantations when these are performed in separate operations. The combination of neonatal deafening, controlled electric stimulation through CIs and longitudinal neural recording in awake animals offers a powerful new approach for studying the developmental plasticity of the binaural system. Specific Aim 2 is to test a new approach for overcoming the severe degradation in ITD sensitivity observed at the high carrier pulse rates used in today's speech processors by introducing additional carrier pulses so as to create short interpulse intervals (IPIs). This approach is motivated by our finding that neurons that short IPIs in irregular pulse trains can restore firing and ITD sensitivity in neurons that ony respond to the onset of high-rate periodic pulse trains. Neural and perceptual ITD sensitivities will be compared with and without short IPIs for both simple pulse trains and modulated pulse trains resembling the current waveforms produced by CI processors with speech syllable inputs. Together, these aims will increase our basic understanding of how stimulation parameters and early auditory experience shape performance with bilateral CIs. They will likely lead to new processing strategies and rehabilitation procedures for bilateral CIs that work better in everyday acoustic environments with spatially separated sound sources, and that are adapted to the history of auditory experience and deprivation of individual deaf patients.

DESCRIPTION (provided by applicant): This proposal extends for a period of five years an interdisciplinary doctoral program begun in 1992 that prepares scientists for innovative research careers in the Speech and Hearing Sciences. Training is intended to enhance markedly the leadership potential of Speech and Hearing researchers within both academia and industry. The basic premise of the program is that today's speech and hearing scientists must be fluent in a variety of physical, biological, clinical and cognitive science disciplines to achieve the multidisciplinary advances that drive innovation. The keystone of the program is a quantitative approach to understanding these four aspects of speech and hearing. The program draws upon the combined expertise of the faculties of Boston area institutions, including the Harvard Medical School and its teaching hospitals, MIT and Boston University. To date, over 140 students have entered the pre-doctoral training program, including some with independent support. These trainees have diverse undergraduate backgrounds in the physical, engineering, biological or cognitive sciences, including some with traditional speech and hearing backgrounds. Training combines coursework and research for the first 3 years after which it concentrates on thesis research, with the Ph.D. degree expected after 4 to 6 years. The coursework and research training combines a broad exposure to the many scientific disciplines relevant to speech and hearing together with a deep understanding of the student's chosen specialty. An intensive clinical exposure is the third major part of the didactic training program. Special attention is given to issues of integrity and responsible conduct of research. Virtually all of our 79 graduates are pursuing careers in health related research, and two- thirds have primary activities in the speech and hearing sciences. Many have faculty positions in basic science, engineering, and clinical departments and are successfully competing for research grants. Some are combining research careers with clinical practice in otology, audiology or speech-language pathology. Some are taking leadership roles in industries related to speech and hearing or in the broader biotechnology field where they are developing assistive devices and treatments for communication disorders. We will continue vigorous efforts to attract highly qualified students, especially from under-represented minorities. PUBLIC HEALTH RELEVANCE: This innovative interdisciplinary doctoral program trains researchers in Speech and Hearing by combining broad exposure to relevant basic science and engineering disciplines, with rigorous expertise in at least one research area, and intense exposure to clinical practice. The program's graduates are taking on leadership roles in academia and industry where they work at the forefront of scientific discovery and develop novel assistive devices and remediation strategies for those affected by disorders of hearing, voice, speech, language and balance. Some are combining research careers with clinical practice in otology, audiology or speech- language pathology.