Barry G. Green, Ph.D. - US grants

Psychophysical research on the human senses has tended to slight the cutaneous senses (tactile and temperature), when it comes to their capacities to function over the life span. The goal is to examine five fundamental (and largely mutually independent) measures of cutaneous sensitivity, over the whole body surface, and from childhood to old age. The five types, all implicated as age-related by background research and pilot data, are: (1) spatial acuity (alignment threshold), (2) error of point localization, (3) texture discrimination, (4) absolute thresholds to warming and cooling, and (5) absolute thresholds to high-frequency vibration. State-of-the-art, forced-choice, psychophysical procedures will be brought to bear throughout. The somatic profiles of tactile sensitivity therewith constructed will help to elucidate two basic issues: (a) Does aging influence these five types of sensitivity uniformly or differentially? (b) Does aging affect all body regions uniformly or differentially? Preliminary evidence favors the working hypotheses that (1) all five types may suffer impairment but in varying degrees, and that (2) the more peripheral the region, the greater may be the toll taken by aging. Measurement will address primarily the gradual changes characterizing the normal aging process. They may nonetheless have important secondary implications for other age-related human conditions, whose study in turn may also reciprocally help to characterize normal aging. Four of these will come under study: (1) spatial acuity and texture discrimination in blind persons of various ages, and the relation of age-related changes in cutaneous sensitivity to the speed of braille-reading; (2) the effects of chronic cigarette smoking on cutaneous sensitivity and the possible recovery after quitting; (3) the manifestation of long-term occupational exposure to vibration on cutaneous sensitivities of patients with Hand-Arm Vibration Syndrome (and a sub-set of these patients who are also diabetic); and (4) the relation of habitual physical activity and fitness to peripheral circulation and cutaneous sensitivity, especially in older persons.

DESCRIPTION (adapted from the applicant's abstract) The PI recently discovered that areas of skin can be found that lack sensitivity to warmth. These surprisingly large (5 sq.cm.), warmth-insensitive fields (WIFs), which are indifferent to heating below 41C, contradict the view that macroscopic warm stimuli can be sensed everywhere on the skin and imply that cutaneous innervation by low-threshold warm fibers can be remarkably sparse and irregular. The PI states that the discovery of WIFs illustrates the need for a reanalysis of the spatial distribution of warmth sensitivity using modern methods of psychophysical measurement and temperature control. Accordingly, the first goal of his project is to study the topography of warmth sensitivity in different body regions and across individuals, and to determine how differences in the spatial density and distribution of warmth may contribute to regional and individual differences in perception of macroscopic stimuli. The second goal of this project is to investigate the extent to which warmth topography may change over time. Early maps of punctate thermal sensitivity were inherently variable, and preliminary data suggest that over periods of weeks or months, sensitivity can develop within previously identified WIFs. The third goal of his project is to take advantage of the extraordinary opportunities WIFs provide to study heat nociception and cold perception directly, independent of afferent activity in the warmth sense. The PI proposes experiments that will use WIFs to investigate basic psychophysical properties of these two systems and to address long-standing questions about the possible contribution of the low-threshold warmth system to the perception of cold, heat, and heat pain. Overall, the proposed studies should yield novel psychophysical data that have the potential to change current thinking about the spatial organization and functional characteristics of human thermal sensitivity. In addition, studies of regional and individual differences in warmth topography and of the contribution of the warmth system to heat and heat pain will provide information essential to the use and interpretation of thermal sensitivity in clinical assessments of peripheral neuropathy.

[unreadable] DESCRIPTION (provided by applicant): Food selection and ingestion depend critically upon the sensory modalities of the mouth. The long-term goal of this project is to understand how the somatosensory and gustatory systems work together to serve these vital functions. Results obtained during the current funding period have provided new information about the kinds of perceptual interactions that do and do not occur between these systems as well as the psychophysical factors that underlie them. Hypotheses generated from these results will be further developed and tested in 4 specific aims. Aim 1 will investigate the effect of "active" versus "passive" tasting on perception of taste, oral somesthesis, and their perceptual interactions. Normal tasting is an active process that occurs within the context of correlated mechanical stimulation, yet taste perception has been studied almost exclusively as a passive reception of chemical stimulation. Experiments will test hypotheses that the ability to perceive some taste stimuli (particularly glutamates), chemesthetic stimuli (chemicals that produce burning or stinging sensations) and tactile stimuli (viscosity, astringency) depends on the mode of tasting and where in the mouth stimulation occurs. Aim 2 will test the hypothesis, based on new findings, that individual differences in taste perception are independent of individual differences in somatosensory perception, and that taste sensitivity is better assessed by use of a prototype taste stimulus (e.g., sucrose) than by the widely used bitter tastant PROP, to which many individuals are aguesic. Aim 3 will provide further tests of a hypothesis, based on recent findings, that bitter taste and burning 'pain' have a close perceptual relationship that arises from their common function as sensory signals of potentially harmful stimuli. Finally, aim 4 will combine psychophysical measurements with fMRI to study the central neural processing of taste and chemesthesis. The proposed study includes tests of specific hypotheses about the relationship of bitter taste to chemesthesis and the presence of a central neural 'gain' that contributes to individual differences in taste but not somatosensation. By providing new data on the perceptual properties and neural basis of normal taste, oral somesthesis, and their interactions, the proposed studies have the potential to improve clinical assessment of gustatory and oral sensory pathologies (e.g., 'burning mouth syndrome') as well as to provide new insights into their possible causes. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): There is no more vital sensory function than guiding and motivating the selection and consumption of safe and nutritious foods. Much of this function is carried-out by the sensory systems of the mouth and nose which together give rise to the flavor of foods. Although research has focused almost exclusively on the senses of taste and retronasal olfaction, also important are the thermal, mechanical, and chemesthetic components of flavor. The long-term goal of this project is therefore to understand in what ways and via which mechanisms somatosensory stimuli contribute to flavor perception. As in past funding periods, psychophysical studies in the current period have led to the discovery of previously unrecognized effects of temperature and touch on taste and chemesthesis. The proposed project will focus on differential effects of temperature on sweet taste, bitter taste, and oral chemesthesis that have implications for the molecular and cellular mechanisms of gustatory and chemesthetic transduction. Specifically, Aim 1 will test the hypothesis that temperature affects sweet taste primarily by modulating the rate and degree of adaptation, possibly by changes in conformation of the T1R2- T1R3 sweet taste receptor. Aim 2 will investigate the potential role of the cation channel TPRM5 in the perceptual phenomenon of Thermal Taste and its possible contribution to the counteraction of sweet taste adaptation. Aim 3 will investigate the differentia effects of temperature on bitter taste perception with the goal of determining the relationship of these effects to different modes of bitter taste transduction, including the possible contribution f TRPM5. Finally, Aim 4 will measure how temperature influences the taste and chemesthetic sensations of salts and acids with the specific goal of testing the hypothesis that their chemesthetic qualities are evoked primarily via different thermally-sensitive TRP channels (i.e. TRPV1 vs. TRPA1). Together these aims will lead to a more complete understanding of the ways in which temperature affects taste and flavor, while also providing unique tests of hypotheses about chemosensory mechanisms in humans that have been developed primarily in animal models. Translational research of this kind is therefore important for advancing our understanding of cellular and molecular mechanisms in humans that could lead to new strategies for addressing dysfunctions of taste and flavor that adversely affect diet and health.

PROJECT SUMMARY How the vital nutrients of salt and water are sensed is not fully understood. This project will investigate these two questions in humans based upon preliminary data that suggest sodium (Na+) in saliva is an important factor in the mechanisms for sensing both nutrients. This possibility first came to light via a chance finding that exposing the tongue tip to water prior to tasting NaCl interfered with perception of saltiness and increased perception of NaCl's sweet and sour side-tastes. A subsequent experiment indicated that these effects could be counteracted by adding NaCl to water in concentrations similar to Na+ in saliva. These results provide the first evidence that salivary Na+ may be important for encoding the quality of salt taste in humans and raises the possibility that rapid dilution and rinsing of salivary Na+ from the mouth serves as a gustatory signal for water. A preliminary fMRI study has supported this hypothesis by showing that adding salivary concentrations of Na+ in the form of NaCl markedly reduces the normal brain response to water, particularly in gustatory cortex. Together these data suggest that Na+ in saliva provides a steady-state gustatory signal from which positive deviations are consistent with the arrival of salt, and negative deviations signal the arrival of pure water. We will build upon the preliminary data to test this overarching hypothesis via 3 specific aims: Aim 1 will determine if salivary Na+ facilitates encoding of NaCl saltiness rather than its side-sides tastes by measuring the taste quality and intensity of suprathreshold NaCl after exposure to pure water compared to after exposure to water containing NaCl and/or NaHCO3. KCl and KHCO3 will also be tested to rule-out osmolarity as a factor, and Na+ in unstimulated saliva will be measured (here and in Aims 2 & 3) to determine if salivary Na+ contributes to individual differences in perception of the NaCl side-tastes. Aim 2 will investigate the peripheral mechanisms and perceptual properties of the sweet and sour side-tastes using lactisole to block activity in the sweet taste receptor TAS1R2/TAS1R3 and amiloride to block the sodium channel ENaC. Finally, Aim 3 will use fMRI to test the hypothesis that the gustatory brain response to pure water depends on rinsing salivary Na+ from the tongue by measuring the response to water with and without a wide range of NaCl concentrations that encompass salivary levels of Na+. KCl will again be tested to rule-out osmolarity as a factor, and amiloride will also be used to block ENaC to determine if the gustatory brain response to water depends upon Na+ signaling via this channel.