Michael G. Heinz - US grants

DESCRIPTION (provided by applicant): The proposed neurophysiological experiments are motivated by two fundamental aspects of sound-level encoding that are strongly affected by cochlear damage and that currently provide significant challenges for the design of effective hearing aids. (1) Loudness recruitment represents the reduced dynamic range and abnormal loudness growth present in almost all hearing-impaired persons with cochlear damage. It is often assumed that loudness is related to the total neural activity evoked by a sound; however, the nature of this relation remains unclear in normal and impaired ears. One aim is to systematically characterize the growth of neural activity with increasing stimulus level in a population of auditory-nerve (AN) fibers for normal and hearing-impaired cats. Stimuli are based on typical psychophysical studies that measure loudness recruitment, and include tones, broadband noise, speech, and masked tones. (2) Robust spectral-shape encoding of complex acoustic stimuli is necessary for many basic auditory functions that underlie communication. A significant enhancement in the representation of speech has been reported in the transformation from the AN to the cochlear nucleus (CN) in normal-hearing animals. The second aim is to compare spectral-shape encoding in the CN of normal and hearing- impaired cats. Two methods will be used to evaluate the relative-level sensitivity for encoding spectral shape in the different cell types of the ventral CN. The data collected will improve the understanding of how cochlear damage affects the neural representation of sound, and will provide useful information for the design of new hearing-aid strategies to overcome loudness recruitment while maintaining and enhancing spectral representation.

DESCRIPTION (provided by applicant): Speech perception by listeners with normal hearing is robust across a wide variety of conditions, whereas people with sensorineural hearing loss (SNHL) typically show much less robust speech perception. The long term goal of these studies is to understand the neural information and neural mechanisms that underlie robust speech perception in order to guide the development of novel strategies for auditory prostheses, which currently have particular difficulty restoring normal speech perception in adverse conditions. The proposed experiments focus on the idea that nonlinearities in auditory-nerve (AN) spatio-temporal response patterns, which are associated with nonlinear cochlear tuning and are produced by the physiologically vulnerable outer hair cells, may contribute to robust speech coding. If true, this result would suggest the need for novel strategies for hearing aids, which currently do not attempt to restore normal spatio-temporal patterns in the AN. Two specific aims focus on the effects of SNHL on enhancements that occur between the AN and cochlear nucleus (CN) in the coding of both spectral and temporal-envelope modulations, two important properties of speech signals. First, spectral coding will be evaluated by measuring the responses of AN fibers and CN neurons to vowel-like stimuli with important spectral features shifted near the best frequency of each neuron. Responses will be measured as a function of level, both in quiet and in background noise, to evaluate robust speech coding in cats with normal hearing and in cats with a noise induced hearing loss. The potential for nonlinear spatio-temporal response patterns to enhance speech coding will be evaluated based on responses of a simple cross-frequency coincidence detector predicted from measured AN responses. Second, the effects of SNHL on the robustness of temporal-envelope coding will be evaluated by quantifying temporal and spectral representations of the fundamental frequency (F0) from the vowel responses collected in Aim 1. If different effects of SNHL on periodicity and temporal-place measures of F0 were observed in the AN and CN, this result would constrain the possible neural mechanisms underlying enhanced envelope coding in the CN as well as perceptual theories of voice-pitch coding. The difficulty hearing-impaired listeners have in understanding speech in complex acoustic environments may be due in part to a reduced ability to segregate sound sources based on voice pitch.

DESCRIPTION (provided by applicant): A great challenge in diagnosing and treating hearing impairment comes from the fact that people with similar degrees of hearing loss may have different speech recognition abilities. Previous research has established that common forms of hearing loss arise from a mixture of inner- and outer-hair-cell damage. A conceptual framework that inner and outer hair cells contribute to hearing in fundamentally different ways motivates the general hypothesis that differences in the degree of inner- and outer-hair-cell dysfunction contribute to across-patient variability in speech perception. Recent psychophysical studies have suggested that listeners with sensorineural hearing loss have a reduced ability to use temporal fine-structure cues in speech perception. These studies have fueled an active debate about the role of temporal coding in normal and impaired hearing, and may have important implications for improving the ability of hearing aids and cochlear implants to restore speech perception in noise. The proposed neurophysiological experiments will provide valuable data by directly quantifying the effects of sensorineural loss on temporal coding in the auditory nerve. The effects of selective inner- or outer-hair-cell damage will be studied using ototoxic drugs. Noise-induced hearing loss will be used to study the more common case of mixed hair-cell damage. Histopathological analyses and functional response measures will be used to characterize hair-cell lesions in individual animals. Specific Aim 1 is to quantify the effects of selective hair-cell damage on within- and across-fiber temporal coding. Innovative analyses that avoid previous experimental limitations in the study of across-fiber temporal coding will be used to quantify fine-structure and envelope coding, as well as traveling-wave delays. Preliminary data support our hypothesis that sensorineural loss affects across-fiber coding of fine-structure more than within-fiber coding. Specific Aim 2 is to determine whether sensorineural loss affects neural coding of fine-structure and envelope cues in vocoded speech. Differences in the ability to understand vocoded speech between listeners with normal and impaired hearing have been used to suggest a perceptual deficit in the use of TFS cues. The physiological basis for these perceptual results is difficult to evaluate because narrowband cochlear filtering limits the ability to isolate fine-structure and envelope at the output of the cochlea. Neural cross-correlation coefficients will quantify directly the effects of sensorineural loss on the fidelity of fine-structure and envelope coding for vocoded speech in noise. Modeling supports the hypothesis that significant degradations occur in both fine-structure and envelope responses. Specific Aim 3 is to quantify the effects of sensorineural loss on temporal coding of fundamental frequency in concurrent complex tones. Listeners with hearing loss show a reduced ability to make use of voice-pitch differences to segregate two competing talkers. It is hypothesized that the ability to estimate the fundamental frequencies of two concurrent complex tones is degraded primarily due to the loss of temporal fine structure, rather than from degraded envelope coding of unresolved harmonics. PUBLIC HEALTH RELEVANCE: The long-term goal of the proposed work is to obtain a better understanding of the physiological bases for robust speech perception, which has important theoretical and clinical implications. The data collected in the proposed experiments will provide fundamental knowledge about the differential effects of inner ear damage on the neural coding of perceptually relevant sounds. This knowledge will benefit the development of diagnostic and rehabilitative strategies to improve the daily lives of people with hearing loss.

PROJECT SUMMARY/ABSTRACT There is a national need to advance the understanding of hearing in both healthy patients and those with various causes of hearing loss. The objective of the proposed program is to train the next generation of faculty who could populate colleges of science, engineering, and health sciences, as well as to send graduates into in order to advance auditory neuroscience training, this new graduate program will leverage faculty expertise in basic hearing science and technology development, from three Purdue University colleges (Science, Engineering, and Health & Human Sciences) and 6 doctoral admissions programs. Two types of investigators are included in the training program: 10 hearing scientists with focused research programs related to auditory system neuroscience, and 7 technology innovators who are trained in other disciplines (electrical, computer and biomedical engineering, and chemistry). Collectively and collaboratively, the program will expand knowledge about mechanisms at the molecular, cellular and systems levels that underlie auditory information processing. This fundamental knowledge can then be applied to better understand the changes that lead to pathologies of the auditory system due to damage, disease, aging, and congenital disorders, as well as understanding how hearing evolved and influences behavior and natural selection. Technological approaches to these questions include, but are not limited to, fluorescent sensors to detect purinergic signaling in the intact nervous system, biological implants for neuromodulation, high-resolution four-dimension calcium imaging deep in the mammalian brain, optogenetics and robotics (automated patch-clamping) for brain circuit analysis, and industry prepared to work toward creative solutions for treating hearing loss. Specifically, This training program is unique in that it is specifically designed to serve students with undergraduate degrees in the disparate disciplines of life science, physical science or engineering, and merge them into a unified cohort focused on auditory neuroscience. Students will be selected for a 2-year term on the training grant, beginning at the start of their second year. The training curriculum includes 3 core courses (one each in neuroscience, the auditory periphery, and signal processing), several recommended courses (e.g., in neurosurgery or neuroscience), a weekly Hearing Science seminar series, and yearly attendance at extramural hearing-related courses and/or auditory neuroscience conferences. In addition to administrative support for the program, the Purdue Institute for Integrative Neuroscience will provide students with additional resources, such as supervised grant writing, hands-on training in animal behavior and human stem cells, annual neuroscience retreats, and access to in-house competitions for travel grants and pilot funding for collaborative projects. Further, this program builds on Purdue's extensive history in training graduate students in collaborative research (particularly in hearing science and technology development), and preparing these students for successful research careers in academia, industry and the clinic. multimodal brain imaging methods.