Stimulus-induced increase of taste responses in the hamster chorda tympani by repeated exposure to 'novel' tastants.

Variations in amplitude of responses of the chorda tympani to repeated application of various novel tastants were measured in familiarized and control groups of adult hamsters. Three groups of 10 hamsters were pre-exposed to 5 mM dulcin, 50 mM potassium L-glutamate (KGlu) or 1 mM 5'guanosine monophosphate (5'GMP). In the fourth group, the tongue was rinsed with 5'GMP for 20 min just prior to recording from the chorda tympani. The tastants were novel to the fifth group (naïve control). A series of 17 stimuli was repeated six times and responses were quantified relative to the initial response of each of the 50 hamsters. The responses of the chorda tympani increased with repetition in the control group. In contrast, no increase in amplitude of response to the pre-exposed tastants or to stimuli with qualitatively related tastes was observed in the group familiarized with either KGlu or 5'GMP. These results indicate that the response of the chorda tympani depends on previous exposure to a tastant. The sensitivity of taste cells appears to be modulated, possibly by stimulus-induced supplementary receptors.

Time-intensity evaluation of acid taste in subjects with saliva high flow and low flow rates for acids of various chemical properties.

The role of the chemical properties of sour stimuli and the role of the human saliva flow rate on acid perception were investigated in 11 high saliva flow rate (HF) and 11 low saliva flow rate (LF) subjects with a continuous stimulus delivery flow rate of 3.2 ml/min and using the time-intensity technique for perception recording. Continuously measuring the pH on the tongue surface on three HF and three LF subjects showed that HF subjects' saliva decreased the acidity of the acid solution more efficiently than the LF subjects' saliva did. However, HF subjects exhibited higher perceived intensity for acid solutions than LF subjects. At equal pH, the order of the efficiency of acids indicated that HCl was the least efficient acid stimulus and acetic acid the most efficient. At equal concentration, the order of efficiency was the opposite (citric acid > malic acid > lactic acid > acetic acid), indicating that titratable acidity rather than pH has to be considered when comparing weak acids. At high concentrations, the ratio of relative efficiency is more in favor of the hydrophobic than the hydrophilic acid in HF subjects compared with LF subjects, i.e. HF subjects are more sensitive to hydrophobic stimuli. Hydrophobic molecules may diffuse more easily into the epithelium of HF than LF subjects, and reach more efficiently trigeminal nerve endings in addition to taste receptor cells.

Decreased taste sensitivity in cancer patients under chemotherapy.

GOALS OF WORK: The aim of the study was to measure taste thresholds among cancer patients under chemotherapy compared to controls. PATIENTS AND METHODS: The study was performed with 110 cancer patients and 170 healthy subjects of similar age distribution were included in the study. The electrogustometric detection threshold was evaluated as the lowest current intensity perceived by the subject in three tongue sites independently with a constant current generator. MAIN RESULTS: Taste thresholds for all cancer patients demonstrated significantly higher values compared to controls. CONCLUSIONS: Cancer patients treated by chemotherapy demonstrated a temporary taste sensitivity deficit. Associated with the illness due to the treatment, this deficit explains the patients complaining of "abnormal or bad tastes", which results in food aversion and has a negative impact on nutritional status and quality of life. In order to prevent the risk of anorexia and the enhanced morbidity related to this deficit, treatment should include relevant information to the subject for anticipating objective taste modifications and a psychological follow-up during the actual change of taste quality perceptions in everyday life.

A new specific ageusia: some humans cannot taste L-glutamate.

A new specific ageusia was found in human subjects for monosodium L-glutamate (MSG). Four tests were successively applied to discriminate non-tasters and hypotasters from tasters. (i) NaCl and MSG thresholds, and (ii) suprathreshold sensitivity were evaluated using the up-and-down procedure. Only 73% of 109 subjects common to both tests demonstrated a sensitivity for MSG significantly higher than their sensitivity to NaCl, and hence a specific sensitivity to L-glutamate. The remaining 27% who showed no significant difference in sensitivity to MSG and NaCl solutions were considered as putative hypotasters. (iii) Perception profiles (time-intensity) for MSG and NaCl were tested in 58 subjects and appeared significantly different in 47 tasters (81%). This technique helped in identifying among putative hypotasters of tests 1 and 2 a few tasters who perceived equal intensity for isoconcentration of NaCl and MSG but who could discriminate isomolar solutions on other cues. Thus, 19% of subjects, for whom no significant differences were found between MSG and NaCl time-intensity profiles, remained in the hypotaster group. (iv) A discrimination task including 24 triangular presentations per subject of NaCl and MSG 29 mM applied to the eight most severe hypotasters showed that two subjects at least (two of 58; 3.5%) could not discriminate between both stimuli. Moreover, these subjects probably perceived identical sensations for MSG and NaCl solutions. The six other hypotasters (10.3%) could discriminate both stimuli at the limit of significance. None of these eight subjects were able to identify the typical umami taste in 29 mM MSG.

Interaction of gustatory and lingual somatosensory perceptions at the cortical level in the human: a functional magnetic resonance imaging study.

The present study has investigated interaction at the cortical level in the human between two major components of flavor perception, pure chemical gustatory and lingual somatosensory perception. Twelve subjects participated in a functional magnetic resonance imaging study and tasted six stimuli, applied on the whole tongue, among which four were pure gustatory stimuli (NaCl, aspartame, quinine and HCl, pH 2.4 or 2.2) and two were both taste and lingual somatosensory stimuli, i.e. somato-gustatory stimuli (HCl, pH 1.6 or 1.5, and aluminum potassium sulfate). Functional images were acquired with an echo planar sequence on a 3 T system and were individually processed by correlation with the temporal perception profile. Both sets of stimuli showed activation in the same cortical areas, namely the insula, the rolandic operculum (base of the pre- and post-central gyri), the frontal operculum and the temporal operculum, confirming a wide overlap of taste and lingual somatosensory representations. However, the relative activation across areas and the analysis of co-activated areas across all runs for each set of stimuli allowed discrimination of taste and somatosensory modalities. Factor analysis of correspondences indicated different patterns of activation across the sub-insular and opercular regions, depending on the gustatory or somato-gustatory nature of the stimuli. For gustatory stimuli different activation patterns for the superior and inferior parts of the insula suggested a difference in function between these two insular sub-regions. Furthermore, the left inferior insula was co-activated with the left angular gyrus, a structure involved in semantic processing. In contrast, only somato-gustatory stimuli specifically produced a simultaneous and symmetrical activation of both the left and right rolandic opercula, which include a part of the sensory homunculus dedicated to the tactile representation of oral structures.

Human taste cortical areas studied with functional magnetic resonance imaging: evidence of functional lateralization related to handedness.

Whole-brain functional magnetic resonance imaging was used to detect local hemodynamic changes reflecting cortical activation in five left handed and five right handed human subjects during bilateral stimulation of the tongue with various tastes. Activation was found bilaterally in the insula and the perisylvian region. These regions correspond to the primary taste cortical areas identified with electrophysiological recordings in monkeys and suggested from former clinical observations in human subjects. Moreover, a unilateral projection was described for the first time in the inferior part of the insula of the dominant hemisphere, according to the subject's handedness.

Cross-adaptation and molecular modeling study of receptor mechanisms common to four taste stimuli in humans.

Psychophysical cross-adaptation experiments were performed with two carbohydrates, sucrose (SUC) and fructose (FRU), and two sweeteners, acesulfame-K (MOD) and dulcin (DUL). Seven subjects were asked to match concentrations that elicited the same intensity as a sucrose reference (30 g/l). Cross-adaptation levels were calculated as the ratio of isointense concentrations measured for a given stimulus before and under adaptation. On average, cross-adaptation between SUC and FRU is low and apparently reciprocal. By contrast, cross-adaptation between SUC and MOD is clearly non-reciprocal: SUC adapts MOD significantly (24%, P < 0.005), but MOD fails to adapt SUC (2%, P < 0.79). Significant and reciprocal cross-enhancement is observed between DUL and MOD (approximately -20%, P < 0.03), and also between SUC and DUL (approximately -15%, P < 0.08). In parallel, molecular modeling of the four tastants was performed in order to look for the 12 common binding motifs that were isolated on 14 other tastants in a previous study. SUC and FRU each display 10 out of the 12 binding motifs, whereas DUL and MOD only display four and five distinct motifs respectively and do not have any motif in common. Experimental cross-adaptation levels seem to correlate well with the number of motifs that molecules have in common. FRU and SUC share a majority of binding motifs and correlatively show mutual cross-adaptation. Four motifs of MOD are found among the 10 motifs of SUC, which may explain why SUC cross-adapts MOD but not vice versa. By contrast, DUL and MOD do not share any motif and do not cross-adapt. The various molecular mechanisms that may be responsible for cross-adaptation and/or cross-enhancement are discussed in light of our results.

fMRI study of taste cortical areas in humans.

We used 3 Tesla functional magnetic resonance imaging (fMRI) with echo planar imaging to map taste projections in the human. Activations were found surrounding and buried in the sylvian fissure; the upper part of insula, the frontal operculum, and the foot of the pre- and postcentral gyri were usually activated. Moreover, we could describe, for the first time, a lateralized associative projection located in the lower part of the dominant hemisphere of the subject (n = 10). We also observed activations in the anterior cingulate gyrus, the centromedial thalamus, and other areas related to emotional or cognitive processes. Thirty subjects were submitted to a familiarization experiment sampling neophobic and nonneophobic stimuli. Measurements of isointense concentrations, magnitude estimates and hedonic values were assessed repetitively for 10 weeks. Five subjects performed 3 fMRI experiments, before, during and after familiarization. Psychophysical data showed a relationship between the evolution of the hedonic assessment and the intensity of the perception, and fMRI results showed a relationship between the evolution of the hedonic assessment and the evolution of the percent of activated pixels in taste cortical area.

Functional lateralization of human gustatory cortex related to handedness disclosed by fMRI study.

Ten healthy subjects aged 20-25 including five right-handed and five left-handed according to the Dellatolas test participated in this functional magnetic resonance imaging (fMRI) study. A 3 Tesla whole-body MR scanner allowed echo planar imaging (EPI)-64 x 64 pixels, repetition time (TR) = 6 s, field of view (FOV) = 20 x 20 cm2--associated to acute anatomical localization of activated foci (256 x 256 pixels). Subjects were bilaterally stimulated with NaCl 85 mM, aspartame 2 mM, quinine hydrochloride 1 mM, glycyrrhizic acid 0.5 mM, guanosine monophosphate 1 mM and D-threonine 250 mM alternating with water. Stimuli and rinse were continuously pushed as bolus of 50 microliters every 3 s to the subject's mouth through microsyringes. We detected brain activated areas by correlation of the MR signal to an on-line perception profile recorded for each experiment and each subject with the finger-span method. We found most activations in the insula and the perisylvian region in agreement with previous electrophysiological studies on monkeys and clinical reports in humans. The superior part of the insula was bilaterally activated, in accordance with a whole-mouth stimulation. A striking lateralization related to handedness was found in a lower part of the insula. This projection in the dominant hemisphere, located in the same coronal plane as the upper insular activation, is the first evidence of a functional lateralization of brain processing involved in taste perception.

Latencies in fMRI time-series: effect of slice acquisition order and perception.

In BOLD fMRI a detailed analysis of the MRI signal time course sometimes shows time differences between different activated regions. Some researchers have suggested that these latencies could be used to infer the temporal order of activation of these cortical regions. Several effects must be considered, however, before interpreting these latencies. The effect of a slice-dependent time shift (SDTS) with multi-slice acquisitions, for instance, may be important for regions located on different slices. After correction for this SDTS effect the time dispersion between activated regions is significantly decreased and the correlation between the MRI signal time course and the stimulation paradigm is improved. Another effect to consider is the latency which may exist between perception and stimulus presentation. It is shown that the control of perception can be achieved using a finger-spanning technique during the fMRI acquisition. The use of this perception profile rather than an arbitrary waveform derived from the paradigm proves to be a powerful alternative to fMRI data processing, especially with chemical senses studies, when return to baseline is not always correlated to stimulus suppression. This approach should also be relevant to other kinds of stimulation tasks, as a realistic way of monitoring the actual task performance, which may depend on attention, adaptation, fatigue or even variability of stimulus presentation.

Multiple human taste receptor sites: a molecular modeling approach.

Numerous experimental data on the human peripheral taste system suggest the existence of multiple low-affinity and low-specificity receptor sites which are responsible for the detection and the complete discrimination of a very large number of organic molecules. According to this hypothesis, a given molecule interacts with numerous taste receptors and vice versa. Statistical analysis of taste intensities estimated by 58 human subjects for various molecules enables the calculation of taste intermolecular distances. For the present modeling study, we hypothesized that a short taste distance (i.e. taste similarity) between two distinct molecules indicates that they bind with similar distributions of affinities to the taste receptors, and hence display similar binding motifs. In order to find common molecular binding motifs among 14 selected organic tastants, hydrogen-bonding and hydrophobic interaction properties were mapped onto their molecular surfaces. The 14 surfaces were then cut in 240 fragments, most of which were made up of 2-4 potentially interacting zones. A correspondence index was defined to measure the analogy between two optimally superimposed fragments. The 75 most representative fragments were all matched pairwise. Twelve distinct clusters of fragments were isolated from the 2775 calculated comparisons. These 12 fragment types were used to calculate structural similarity distances. We then performed a combinatorial analysis to identify which fragment combination best reconciled structural and taste distances. We finally identified an optimal subset of seven fragment types out of the 12, which significantly and best accounted for the 91 pairwise taste distances between all 14 modeled tastants. These seven validated fragment types are therefore presented as good candidates to be recognized by the same number of distinct taste receptor sites. Potential applications of these identified binding motifs to tastant design are suggested.

Are umami taste receptor sites structurally related to glutamate CNS receptor sites?

Umami tasting substances, MSG (monosodium glutamate), HG (glutamic acid), LGDE (1-glutamic acid diethyl ester), DLHCA (dl-homocysteic acid), DLAAA (dl-aminoadipic acid) and 5'GMP, were tested on the hamster and the human. Ten mM MSG was routinely used in the hamster as it elicited strong chorda tympani responses. Similar response amplitudes were found for MSG, HG, LGDE, DLAAA 10 mM, DLHCA 8 mM and sucrose 100 mM. A 5 microM concentration of 5'GMP eventually was an efficient stimulus on a few preparations. Such a low concentration is very seldom efficient as a taste stimulus in rodents, indicating a higher specificity of receptor mechanisms than what is usually found for sweet taste, for example. The synergy between MSG and 5'GMP was found in the hamster CT only for concentrations lower than those of the literature, i.e., a mixture of 12 microM 5'GMP and 2.5 mM MSG showed a reinforcement of 50% in response amplitude equivalent to a 100% increase in concentration. We take this as an evidence of an umami component in the hamster CT response to glutamate; in accordance with literature data, we could not find reinforcement for higher concentrations which were in fact near saturation. Responses to MSG, HG, LGDE, DLAAA and DLHCA, among 38 other organic stimuli, were studied in 42 hamster chorda tympani. Responses to HG, LGDE and 5'GMP, among chemoreception of these compounds used as umami tasting stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Taste as a highly discriminative system: a hamster intrapapillar single unit study with 18 compounds.

Seventy-nine single units were recorded with glass micropipettes applied onto taste pores of the anterior portion of the tongue in anesthetized hamsters. The receptive field of each recorded unit was located by iontophoretic stimulation applying either anodal or cathodal current (1-20 microA) to a non-stimulating solution of sodium cyclamate (5 mM). Different kinds of responses to iontophoretic stimulation were described. Eighteen chemical stimuli including sweet and bitter tastants for humans, and amino acids were locally applied to one papilla of the receptive field of 63 of these units. Stimulations were applied in a continuous flow (30 ml/min) in a small chamber. Response criterion was chosen as 2 S.D. above the mean activity recorded during the minute preceding the stimulus arrival. The low amplitude of single unit responses to chemicals is discussed by reference to the recording and stimulating techniques and compared to results of control experiments on whole nerve recordings and psychophysical experiments on human subjects. The importance of a high flow rate during continuous flow stimulation was demonstrated. The possible necessity of mechanical stimulation to facilitate taste responses was outlined. The sensitivity of units to stimuli applied either chemically or iontophoretically was not identical. Contrary to authors expectations, localized sensitivities for a few specific chemicals were disclosed. The response reproducibility to chemical stimulation was 84% (S.D. = 1.6%). chi 2 calculation, correspondence analysis and hierarchical clustering showed small distances between the two profiles representing the same stimulus or the two profiles representing the same unit, but great distances between profiles representing either different stimuli or different units. All stimuli are different from one another. Only 6 pairs of similar units were found among 63 units. Unit clusters could be found only if a few stimuli were considered but they vanished when all 18 stimuli were used in the calculation. The breadth of tuning of units ranged from 0.25 to 0.92 with a mean of 0.68. We show that the peripheral taste system is highly discriminative. Each stimulus evokes a distinct sensory image. At least 8 independent factors are needed to describe the peripheral taste space, setting a lower limit to the number of different peripheral information channels (putative acceptors) involved.

Relative sweetness of fructose compared with sucrose in healthy and diabetic subjects.

Fructose is credited with some advantages over sucrose: it causes less of an increment in plasma glucose and insulin response, and the taste is sweeter. We reevaluated the latter property with a new methodology (the "up and down" method adapted from Dixon) in 33 healthy subjects, 17 insulin-dependent diabetes mellitus (IDDM) patients, and 12 non-insulin-dependent diabetes mellitus (NIDDM) patients. Sweetening potency was determined over 2-3 test sessions in each subject. Results are expressed in percent as the relative sweetness (R) of fructose (F) over sucrose (S), taken as reference. In the first set of experiments, with a 30-g/L sucrose-water solution at pH 7, we found that R values were similar for healthy subjects (102 +/- 8%) and diabetic subjects (106 +/- 7%) (P less than .05). No significant difference between IDDM and NIDDM patients was observed. In a second set of experiments, performed in healthy subjects only, R was increased in acid water (114%; P less than .01), in lemon juice (136%; P less than .001), in water at 2 degrees C (130%; P less than .001), and in coffee at 2 degrees C (120%; P less than .02); mean values were decreased in grapefruit juice (77%; P less than .001), in water at 43 degrees C (88%; P less than .01), and in coffee at 53 degrees C (87%; P less than .001). We found that the test methodology had a very satisfactory intrasubject reproducibility (coefficient of variation [C.V.] less than 8%) but a very wide intersubject variability (C.V. congruent to 32%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Factors of quantitative variation in taste sensitivity]. / Les facteurs de la variation quantitative de la sensibilité gustative.

Under well controlled experimental conditions, it is possible to accurately and reproducibly measure taste thresholds as well as supraliminal intensity matches in individual subjects. It is therefore possible to evaluate interindividual differences. Some factors influencing sweetening potencies remain obscure unless individual data are processed. Sweetening potency depends on the taster, the stimulus concentration, pH and temperature, but also on all the components of the mixture into which the sweetener is incorporated.