John F. Brugge, Ph.D. - US grants

Natural sounds, including those used for communication by humans, are complex signals that often contain many frequencies that flucturate in amplitude and time. These fluctuations are known to be information-bearing elements of such sounds and the auditory systems of some animals have apparently evolved mechanisms for their detections and transmission. Auditory cortex of the cat comprises a number of fields that are distinct from one another in structure and function. The primary auditory area (AI) has been studied extensively as regards the mechanisms of processing simple acoustic stimuli. Little is known about the ways that it processes more complex signals such as frequency- and amplitude-modulated signals which are major components of natural sounds. Essentially nothing is known about the development of these mechanisms in early postnatal life when the auditory system is maturing structurally or the effects on them of altered acoustic environments or cochlear lesions. The long term objective of this research is to understand the ways in which auditory areas of cerebral cortex normally process such complex sounds, how this processing develops after birth in a maturing auditory system, and how this processing might be altered by altering the input to the auditory system either by sound conduction blockade or receptor damage. The responses of single auditory cortical neurons are recorded with extracellular microelectrodes in anesthetized animals when controlled complex sounds are delivered to one or both ears. Amplitude- or freqency- modulated tones or noises are the principal stimuli used to mimic some of the salient features of natural sounds. The spatial distribution of neurons sensitive to particular attributes of such sounds is mapped on to the cortex and related to known functional organizations and patterns of anatomical connections. Similar experiments are carried out on animals reared from birth with conductive hearing loss or unilateral cochlear destruction. This work should reveal cortical mechanisms involved in complex sound analysis and thereby help in understanding speech perception problems associated with central nervous system disorders.

The long-range goal of the Program is to gain a thorough understanding of the complex sensory and neural bases of hearing and hearing impairment. The present proposal addresses complementary sets of questions related to a major theme of the Program: neural processing of the natural and spatial location of complex sound. It represents an integrated series of studies featuring novel experimental approaches conduced by a multi-disciplinary team of established investigators who, collectively, bring to the Program a record of productive interaction and expertise in a wide variety of disciplines including neurophysiology, membrane biophysics, neuroanatomy, electronic and computer engineering, statistical analysis, mathematical modeling, physical acoustics, signal processing, and human and animal behavior and psychoacoustics. Experiments are proposed that span cellular, system and behavioral levels. Specifically, the collaborative efforts includes studies of 1) processing speech and complex sounds by the cochlear nuclei, including structure/function studies at the cellular level and complementary animal psychophysics, 2) brainstem mechanisms involved in spatial localization, with special emphases on the precedence effect, the physiology and connectivity of auditory brainstem nuclei, and the coding of auditory spatial cues, 3) auditory cortical mechanisms of spatial hearing, with emphases on encoding sound motion and directional signals in background noise 4) structure/function relationships underlying auditory cortical processing, dealing with intrinsic and synaptic mechanisms and neural circuitry in auditory cortex and 5) human sound localization with emphases on processing of monaural directional cues and cues involved in moving sounds sources. The Program promotes interaction between and among investigators through such means as collaboration on research projects, sharing of core facilities and technical support staff, sharing of computer programs and databases over a network, and participation in regulated and frequent seminars that emphasize informal sharing of ideas and critical evaluation of research in progress. This work constitutes a series of necessary steps in understanding fundamental structure and function of the normal auditory system, which is essential to understanding mechanisms that underlie hearing impairment and to devising new strategies for diagnosis, intervention and treatment of disorders of hearing, speech and language.

The long-range goal of the program is to gain a thorough understanding of the complex sensory and neural bases of hearing and hearing impairment. The present proposal addresses a complementary set of questions related to the major theme of the program: spatial localization of complex sound. These questions are addressed through an integrated series of five studies to be conducted by a multi-disciplinary team of established investigators who, collectively, bring to the program a record of productive interaction and expertise in neurophysiology, neuroanatomy, electronic and computer engineering, behavioral testing and human psychoacoustics. Specifically, the collaborative effort includes studies of 1) the peripheral auditory system, from the external ear to the auditory nerve, with emphasis on theoretical models that are experimentally verified, 2) transformations of complex-sound information in the cochlear nuclear complex, with emphasis on speech processing and structure/function relations, 3) binaural processing of complex sound at the level of the midbrain, with special emphasis on mechanisms that underlie the precedence effect and directional hearing as studied with simulated free-field sound, 4) directional selectivity at the level of auditory cortex, examining the primary field and several surrounding cortical areas using simulated free-field sound and 5) sound localization by human listeners, with emphasis on a listener's knowledge or expectations of sound parameters, on sound motion detection, on segregation of multiple sources and on a neural-net model. The work employs a wide variety of methods, including acoustical measurement, signal processing and simulation, theoretical modeling, single-cell recording, animal behavior, neural track tracing, light- and electron microscopy and human psychophysics. The results of this work will provide an increased understanding of how the normal auditory system encodes information pertaining to complex sounds in space. This work is a necessary step in understanding the pathophysiology of the auditory system and will help give insight into strategies for diagnosis, intervention and treatment of hearing disorders and for developing technically sophisticated aids for the hearing impaired, including hearing aids and cochlear prostheses.

psychoacoustics; health science manpower; biomedical facility; computational neuroscience; auditory stimulus; hearing; electrophysiology; histology;

The overall goal of this research is to understand the auditory cortical mechanisms involved in spatial localization of complex sound. To achieve this goal, we have implemented an earphone delivery system that mimics, at the eardrum of a cat, sound coming from a particular direction in space. The stimulus set constitutes a virtual acoustic space. Using this approach to study directional sensitivity of primary auditory cortical neurons, we propose to pursue four related specific aims. 1) We plan to study the directional sensitivity of AI neurons over a range of signal intensity to test the hypothesis that directional selectivity, as expressed in the timing and discharge strength within a neuron's spatial receptive field, is intensity tolerant. We will do this under both monaural and binaural conditions. We will also study a neuron's directional sensitivity under reverberant conditions that are believed to be involved in determining sound distance. 2) We will study the cortical mechanisms that are involved in processing sound motion. In doing so we will separate the salient cues that give rise to the motion response of AI neurons. 3) We will test the hypothesis that directional sensitivity of AI neurons is relatively insensitive to competing background sounds, using a wide range of background sound condition. 4) Using a theoretical framework based on the theory of maximum likelihood estimation, we will test the upper limit of performance that can be expected from an ideal observer given the information contained in cortical spatial receptive fields. The results will be compared to human psychophysical performance.