Thomas C. Pritchard - US grants

Current theories of quality coding in gustation are based largely upon single neuron data collected in peripheral nerves and the lower brain stem of anesthetized rodents. Thalamic and cortical gustatory areas have been neglected because neurons in these areas are very sensitive to general anesthesia and the technology for chronic recording in rodents is inadequate. The research proposed will circumvent these obstacles by using established techniques for chronic electrophysiological recording in awake, behaving primates. This research represents a logical extension of four primate neuroanatomical experiments completed in this laboratory. These experiments have described the organization of gustatory and visceral afferent systems from the medulla to the cortex. Three forebrain areas that receive gustatory afferent projections will be investigated: the thalamic taste area, insular-opercular cortex, and a small cortical area on the lateral convexity that receives an overlapping projection from the thalamic oral somatosensory relay. Intraoral fluid stimuli will be used to determine: 1) the degree of gustatory, tactile, and thermal specificity of individual neurons in each area; 2) the differential sensitivity of individual neurons to various sapid stimuli; and 3) the ability of individual neurons to respond selectively to complex, behaviorally relevant stimuli. Additional experiments with lightly anesthetized primates, will determine if gustatory cortex is topographically organized and, if so, whether its basis is spatial, chemical or related to specific subpopulations of receptors. These data, in addition to describing normal taste perception, may be relevant to certain pathological types of ingestive behavior (e.g. anorexia nervosa and bulimia) that require cortical involvement.

Separate neurophysiological experiments have shown that neurons responsive to taste and smell stimulation are coextensive within a circumscribed area of the orbitofrontal cortex. Other experiments have shown that this area receives substantial projections from established gustatory and olfactory areas of the brain. Because these previous neurophysiological studies did not test both gustatory and olfactory stimuli, it is not known whether functional integration of taste and smell occurs in the orbitofrontal cortex. This project will use electrophysiological and anatomical techniques to address the following issues: (1) Do the chemosensory neurons in the orbitofrontal cortex comprise a single convergent population, a mosaic of independent olfactory and gustatory elements, or two contiguous, but functionally distinct areas, and (2) Which areas of the brain project to the chemosensory area(s) within the orbitofrontal cortex? These experiments will contribute important information about the functional organization of orbitofrontal cortex, an area of the forebrain that may be relevant to certain pathological types of ingestive behavior (e.g. anorexia nervosa and bulimia) that require cortical involvement.

9413025 Pritchard Taste is a critical sense for animal survival, determining what is good and what is not good to eat. Yet compared with our understanding of other sensory modalities like sight and hearing , we have only a rudimentary knowledge of the gustatory system. Sight, hearing and touch are centrally organized in a hierarchical fashion in the mammalian brain; in particular, the thalamus is a major brain region above the brainstem which processes and integrates sensory information before it gets to the level of the cortex. We have little comparable information on central processing in taste pathways. This project uses novel experiments with sophisticated behavioral tests to see what particular processing occurs in the brainstem, without the contributions from the thalamus. The unique approach will determine whether specific taste deficits represent a sensory loss, a change in behavioral motivation, or a perceptual deficit, each of which could influence taste- guided behavior. These results will provide needed fundamental advances in our understanding of taste; results will be important beyond chemosensory neuroscience, to cognitive and perceptual issues of brain function, and to the food industry.

Understanding normal and dysfunctional body weight regulation requires an elucidation of the factors that initiate, maintain, and terminate an individual meal. Each of these aspects of meal consumption is influenced by oral (gustatory) and post-oral (post-ingestive) factors, whose separate and integrative contributions to satiety are not fully understood. The proposed experiments will focus on the integrative nature of this relationship. Following ingestion and the initiation of digestion, nutrients trigger a variety of post-ingestive signals from upper gastrointestinal and vascular sites that terminate feeding, produce satiety, and reduce the appetitive nature of food. Recent studies have suggested that satiety may be accompanied by a decrement in taste-elicited activity in the orbitofrontal cortex, but the link between post-ingestive feedback and satiety-induced changes in taste responsivity has not been addressed either directly or systematically. The proposed experiments will examine how post-ingestive feedback (gastric distention, duodenal glucose infusion, venous glucose infusion) modulates taste-elicited activity in the orbitofrontal cortex. Collectively, these experiments will provide the first systematic neurophysiological investigation of how gustatory and visceral factors contribute to the etiology of satiety and the control of food intake. These data may expedite development of successful strategies for diagnosis and treatment of various eating and metabolic disorders.

Humans offer an exceptional opportunity for studying hemispheric differences in gustatory processing because their subcortical taste pathway is arranged in a strictly ipsilateral fashion. The demonstration by Pritchard et al. (1999) that language-based taste tasks are performed in the left hemisphere suggests that other aspects of gustatory perception may be lateralized as well. This proposal addresses perception and expression of gustatory perception may be lateralized as well. This proposal addresses perception and expression of gustatory affect, an integral component of taste that is cortically based and reliant on another lateralized gustatory affect, an integral component of taste that is cortically based and reliant on another lateralized system: emotion. Psychophysical techniques will be used to assess gustatory affect in patients with damage to either the rostral insula (primary taste cortex) or the orbitofrontal cortex. The orbitofrontal cortex, which receive direct projections from primary gustatory cortex, has been implicated in perception of emotion contained in facial expression and voices. The proposed experiments will determine the respective contributions of the light and right hemispheres to the perception of gustatory affect. Consistent with other studies in the visual and auditory systems, we expect to find that the left and right hemispheres work in concert but that positive affect (e.g., happiness) is mediated primarily by the left hemisphere while negative affect (e.g., disgust) is processed primarily by the right hemisphere. We will determine if deficits if gustatory affect are independent of deficits in emotional perception in the visual and auditory systems. Patients with insular damage in the left hemisphere are expected to be impaired in naming of taste quality and verbal reports of taste affect. However, the same patients are expected to report taste affect accurately when using other non-language-based techniques that are organized in the right hemisphere. Combining psychophysical taste testing with high resolution (1mm) MRI-based reconstructions of the brain damage in our subjects will enable us to determine with greater accuracy the location of primary taste cortex in humans.