Mark Jude Tramo - US grants

The broad objective of the proposed research is to define the neural mechanisms that govern the perceptual processing of complex sounds at the level of the cerebral cortex. The long-term goal is to develop an experimental model by which to test hypotheses about the role of auditory cortical neurons in feature abstraction, percept formation, and object recognition. Of particular relevance to human health is how these neural mechanisms mediate the discrimination and recognition of complex pitch, timbre, and speech, which are disrupted following injury to auditory cortex. The proposed experiments will be carried out under the direct supervision of the sponsors and will be the focus of an intensive laboratory training experience designed to prepare the principal investigator for a research career dedicated to the study of cortical auditory functions. The specific aims of the proposed research examine the representation of spectral and temporal information in single neurons and in anatomically and biochemically differentiated fields of neurons in primate auditory cortex. The experimental design seeks to apply to the study of cortical auditory functions modern laboratory techniques that have greatly advanced knowledge about the functional anatomy of visual cortex in recent years. These include methods of mapping the distribution of a cellular enzyme subserving oxidative metabolism, measuring regional metabolic activity during stimulus processing, recording single unit activity during stimulus processing, and correlating these physiological properties with the cytoarchitectonic organization of functionally specialized zones.

Auditory pattern perception by human and nonhuman primates is mediated by neurons in superior temporal cortex that alter their electrophysiological behavior in response to acoustic signals (Walzl & Woolsey 1943; Katuski et al. 1962; Celesia 1976; Heffner & Heffner 1986; Tramo et al. 1990; Liegeois-Chauvel et al. 1994; Peretz et al. 1995; Colombo et al. 1996). The proposed research investigates how the distinctive spectrotemporal patterns of different vocal communication signals are encoded in the discharge patterns of auditory cortical neurons. Specifically, the timing and magnitude of neuronal excitation and inhibition will be analyzed in alert Macaca mulatta with respect to the acoustical features and behavioral contexts of species-specific vocalizations. the experimental design takes advantage of 1) homologies between humans and macaques in certain aspects of auditory cortex anatomy and function; 2) the rich vocal repertoire of rhesus monkeys; 3) previous and concurrent characterizations of natural communication behavior and perceptual functions in macaques by the Co-Principal Investigators; 4) the high probability, magnitude, and temporal complexity of neuronal responses to natural sounds in the absence of general anesthesia; and 5) insights gained during our initial experimental observations (Tramo et al. 1996).

DESCRIPTION: Deficits in speech perception and language acquisition with relative preservation of pure tone detection thresholds and other elementary psychoacoustic functions are common findings in diseases afflicting the auditory forebrain. Injury to the peripheral auditory system, especially early in development, often leads to central pathophysiological changes and perceptual impairments that cannot be overcome by prostheses or cochlear implants. The present application seeks to continue the development of our nonhuman primate model for analyzing the physiological response properties of auditory cortical neurons in relation to the acoustical features of communication sounds. Specifically, the timing and magnitude of neuronal excitation and inhibition evoked by species-specific vocalizations and synthetic stimuli will be analyzed in alert Macaca mulatta with respect to: 1) the spectral energy distribution and harmonic structure of the stimulus; 2) the temporal envelope of the stimulus waveform; 3) the temporal separation of stimulus events; 4) the temporal order of stimulus events; 5) the acoustic and contextual categories of vocal stimuli; and 6) the spectrotemporal receptive field properties of the neuron. Microelectrode penetrations into posterior superior temporal cortex will be stereotaxically guided using magnetic resonance imaging; recording sites will be reconstructed histologically after terminal mapping experiments, and microanatomical correlates will be defined using acetylcholinesterase, cytochrome oxidase, parvalbumin, Nissl, and myelin staining methods. In the longer term, this experimental model could be developed to investigate central pathophysiological-functional correlates of acute and chronic peripheral disease and to compare cortical neuron responses to vocal communication sounds before and after cochlear implantation. The aim of research on the single-unit physiology of auditory cortex in relation to the psychophysics of vocal communication is to advance basic knowledge about auditory function in the hope of enhancing treatment strategies for communication disorders that utilize electrical stimulation, prostheses, and rehabilitation therapy.

Deficits in speech perception and language acquisition with relative preservation of pure tone detection thresholds and other elementary psychoacoustic functions are common findings in diseases afflicting the auditory forebrain. Injury to the peripheral auditory system, especially early in development, often leads to central pathophysiological changes and perceptual impairments that cannot be overcome by prostheses or cochlear implants. The present application seeks to continue the development of our nonhuman primate model for analyzing the physiological response properties of auditory cortical neurons in relation to the acoustical features of communication sounds. Specifically, the timing and magnitude of neuronal excitation and inhibition evoked by species-specific vocalizations and synthetic stimuli will be analyzed in alert Macaca mulatta with respect to 1) the spectral energy distribution and harmonic structure of the stimulus; 2) the temporal envelope of the stimulus waveform; 3) the temporal separation of stimulus events; 4) the temporal order of stimulus events; 5) the acoustic and contextual categories of vocal stimuli; and 6) the spectrotemporal receptive field properties of the neuron. Microelectrode penetrations into posterior superior temporal cortex will be stereotaxically guided using magnetic resonance imaging; recording sites will be reconstructed histologically after terminal mapping experiments, and microanatomical correlates will be defined using acetylcholinestcrase, cytochrome oxidase, parvalbumin, Niss1, and myelin staining methods. In the longer term, this experimental model could be developed to investigate central pathophysiological-functional correlates of acute and chronic peripheral disease and to compare cortical neuron responses to vocal communication sounds before and after cochlear implantation. The aim of research on the single-unit physiology of auditory cortex in relation to the psychophysics of vocal communication is to advance basic knowledge about auditory function in the hope of enhancing treatment strategies for communication disorders that utilize electrical stimulation, prostheses, and rehabilitation therapy.