Taste modulation induced by interactions among specific compounds remains poorly understood. L-histidine and creatinine are both bitter compounds abundant in dried bonito dashi. This study investigated whether 10 bitter compounds could shift the taste quality of L-histidine from bitterness toward sweetness, as assessed by sensory evaluation using a fixed-sum method. When presented alone, 4% L-histidine elicited bitterness accompanied by weak sweetness, whereas iso-bitter creatinine evoked predominantly bitterness. Remarkably, pre-stimulation with creatinine shifted the taste quality of L-histidine toward sweetness. Similar effects were observed after pre-stimulation with isoleucine, tryptophan, phenylalanine, and creatine, but not with histidine, valine, leucine, caffeine, or carnosine. This effect was transient, as increasing the interval after creatinine pre-stimulation restored the bitterness of L-histidine. In addition, 0.1% NaCl altered the bitterness-to-sweetness balance of L-histidine toward sweetness after pre-stimulation with creatinine. The taste quality of histidine alone was highly sensitive to pH: bitterness peaked at pH 7.0, whereas sweetness increased under alkaline conditions. In contrast, varying the pH of the pre-stimulation solution between 5.0 and 8.0 did not affect the modulation of L-histidine taste. These findings demonstrate a previously unrecognized histidine-specific form of taste modulation, suggesting interactions among naturally coexisting bitter compounds may dynamically alter taste qualities in traditional broths and other complex foods.
Post-infectious olfactory dysfunction (PIOD) is common in COVID-19 patients. This two-arm double-blinded randomised controlled trial aimed to establish proof-of-concept for Vitamin A versus placebo as a treatment modality for patients with PIOD. This study compared 9000 IU daily self-administered vitamin A intranasal drops versus peanut oil drops over 12 weeks in COVID-19 patients with PIOD. Outcome measures included: olfactory bulb volume (OBV), olfactory sulcus depth, cerebral functional MRI Blood Oxygen Level Dependent (BOLD) signal, Sniffin’ Sticks TDI score, SSParoT, Olfactory Disorder Questionnaire (ODQ) score and Brain Derived Neurotropic Factor (BDNF) levels were collected from participants at baseline and after trial intervention at 12 weeks. Fifty-seven PIOD were recruited in the trial and allocated to Vitamin A or placebo arm at a 2:1 ratio. After withdrawals and exclusions, 30 participants in the Vitamin A arm and 15 in the placebo arm were analysed. There was no significant difference in the change in OBV between both groups. Aside from an improvement in quality-of-life component of ODQ questionnaire scores (p = 0.01), there were no significant differences in any of the other secondary outcome measures. This proof-of-concept trial has demonstrated no significant effect of intranasal Vitamin A on olfactory function in COVID-19 PIOD patients. Further work is required to identify other therapeutic agents in the management of PIOD or evaluate a different PIOD cohort with non-COVID aetiology.
The accessory olfactory system is specialized for detecting chemical cues that elicit innate reproductive, social, and defensive behaviors and physiological responses in mammals. In mice, vomeronasal sensory neurons express three receptor families, type 1 vomeronasal receptors, type 2 vomeronasal receptors, and vomeronasal formyl peptide receptors, that collectively detect diverse semiochemicals, including pheromones, microbe-derived peptides, and predator cues. Recent advances in molecular organization, structural diversity, and ligand specificity have begun to clarify how vomeronasal receptor families encode ethologically relevant chemical signals, thereby providing initial insight into organizational principles of vomeronasal signaling, including labeled-line and integrative coding strategies. Nevertheless, the vast majority of vomeronasal receptors remain functionally uncharacterized, and the molecular logic of sensory coding in this system is still only partially understood. This review synthesizes current knowledge of vomeronasal receptor diversity, ligand recognition, and accessory mechanisms, while highlighting both the progress made and the major gaps that remain in understanding how receptor-derived signals are transformed into adaptive behavioral and physiological responses.
Many animals utilize pheromones as chemical substances that regulate reproductive and social behaviors. Elucidating how diverse pheromonal compounds are detected and translated into specific behavioral and physiological responses is crucial for understanding animal behavior. In vertebrates, pheromone reception is primarily mediated by the vomeronasal organ. Vomeronasal sensory neurons detect a broad range of semiochemical molecules, including pheromones and allelochemicals, and transmit this information via the accessory olfactory bulb to higher brain regions, such as the amygdala and hypothalamic regions. Although recent studies have advanced the identification of pheromonal molecules and the analysis of the neural circuits responsible for their detection, ligands have been identified for only a small fraction of the hundreds of vomeronasal receptors. Analyses of genetically engineered mice lacking key components of vomeronasal signal transduction in vomeronasal sensory neurons have provided comprehensive insights into the relationship between vomeronasal sensory input and behavioral output. This review focuses on pheromones among the semiochemicals detected by the vomeronasal organ and summarizes current understanding of pheromonal perception and associated social behaviors, primarily based on studies in mice, the most extensively investigated model organism to date.
Reliable and standardized assessment of human taste function remains a critical need in clinical and research settings. Here, we pooled individual participants' data of gustatory recognition thresholds from 6 studies (N > 500) that employed a unified methodology combining taste sprays with an adaptive Bayesian algorithm (QUEST) across 4 basic tastes: sweet, salty, sour, and bitter. Thresholds were estimated using a yes-no task format and psychometrically controlled stimuli, enabling efficient and precise estimation across individuals. Results revealed approximately normal distributions of thresholds within each modality, spanning 2 to 3 log units, and modest but consistent correlations between tastes. Gender and age influenced sensitivity, with women generally showing lower (better) thresholds than men, and older adults exhibiting reduced sensitivity, particularly for bitter and sweet tastes. A composite taste score derived from z-standardized thresholds showed stronger age- and gender-related effects than individual modalities, supporting its utility as a general index of taste function. These findings validate the use of the QUEST algorithm for gustatory psychophysics and provide preliminary normative data for taste sensitivity using time-efficient procedures. The consistency of results across studies supports the development of standardized protocols for clinical and population-level taste testing. Future research should extend this framework to broader populations and additional taste qualities to establish comprehensive benchmarks for gustatory health.
The purpose of the study was to develop a self-reporting measure of trigeminal function, addressing the need for the participants' self-perception of comfort and sensitivity related to trigeminal sensations. A 15-item questionnaire was designed and tested on the sample of n = 1,001 participants from the general population in Dresden, Germany, aged from 18 to 86. For validation included were ratings of nasal trigeminal stimuli using ammonium, lateralization of eucalyptol as a measure of trigeminal sensitivity, odor identification, and self-ratings of nasal airflow and olfactory function. Based on factor analyses, the initially intended structure of the questionnaire was revised to improve the tool's overall psychometric quality. Originally intended structure was not well supported. Exploratory factor analysis based on a scree plot indicated 1-factor solution, with the final version comprising 8 carefully selected items, providing the best fit. The questionnaire presented good reliability (Cronbach's α = 0.74) and satisfying validity, based on correlations with other self-reporting measures and group comparisons. Invariance analysis across gender suggested the use of separate norms for men and women. The trigeminal function questionnaire is a brief, reliable and valid measure for assessing self-perception of trigeminal function.
Approach and avoidance behavior towards sensory stimuli serve as powerful behavioral readouts of our mental representations of the external world and our expectations and motivations in navigating it. In the olfactory system, approach or avoidance of odors statistically associated with people, places, and things relate to ecologically critical functions like feeding, fear, and reproduction. However, experimental methods for quantifying approach/avoidance behavior in relative terms across odors have been limited. Here we present a novel method for quantifying mouse approach/avoidance in an open field arena scented with up to four odors simultaneously. In lieu of traditional inferential statistics (which greatly limit the information that can be learned in this multivariate experiment), we demonstrate the a priori definition of quantitative hypotheses for the distribution of time among scented corners and the use of information theory-derived statistical metrics to quantify the relative likelihood of each competing hypothesis given the data collected. Finally, we use data from a fear conditioning experiment to demonstrate the application of this method to conclude that fear conditioned mice exhibit a fear generalization gradient that decreases as odorants become more different from the threat-predictive odorant, as opposed to competing hypotheses that mice are specifically avoiding the threat-predictive odorant or have overgeneralized their fear and avoid all test odors regardless of similarity. Critically, this method takes only a few minutes per animal with no prior behavioral training required, and it can be performed easily without automated apparatus.
Anosmia and hyposmia, referring to total or partial smell loss, respectively, affect 3% to 20% of people. The Sniffin' Sticks Extended Test, assessing odor threshold, discrimination, and identification (TDI), is a well-validated tool widely used in European and US clinics. However, its time and resource demands limit routine use. During the COVID-19 pandemic, several rapid smell tests were developed, yet their classification performance and agreement with established psychophysical measures remain underexplored. We compared 4 alternatives-the Visual Analog Scale for self-rated smell ability (VAS), the smell section of the Appetite, Hunger, and Sensory Perception questionnaire (AHSP), the Global Consortium for Chemosensory Research Smell Check (GCCR-Check), and the SCENTinel rapid smell test-against TDI scores in a longitudinal cohort of 96 adults (77 female patients; age 46.6 ± 10.5 yr) with post-COVID-19 smell dysfunction, assessed up to 5 times over 12 mo. Analyses used Generalized Estimating Equations for repeated measures, Bland-Altman plots for agreement and bias, and area under the receiver operating characteristic (AUC) curves for classification. No tool dominated across all TDI-defined categories. SCENTinel showed robust performance for anosmia (0.81) with the most balanced sensitivity-specificity trade-off among rapid tests, while GCCR-Check achieved the highest AUC for anosmia (0.88) and VAS best identified normosmia (0.73). Agreement analyses revealed systematic biases in self-report and rapid psychophysical tests. Rapid tools reliably detect anosmia, while classification performance decreases near diagnostic boundaries, particularly for normosmia. Combining brief self-report and short psychophysical measures may improve accuracy while maintaining feasibility for clinical and large-scale screening.
The human primary gustatory cortex (hPGC) resides in the insula. How this region processes and represents taste stimuli is still under investigation. Here, we use ultra-high field (7 Tesla) fMRI to investigate whether the insular cortex discriminates the 5 basic tastes (quality) and the perceived valence of the tastes. Eight healthy young volunteers rated the valence (positive, negative, and neutral) of a series of tastants delivered as small liquid boluses via a gustometer during a preliminary off-line intake session. Functional acquisition was set up to fully cover the insular cortex at high isometric spatial resolution. Using multivariate analyses and the searchlight method, multiclass discrimination accuracy for all basic tastes and their rated valence was assessed separately for each participant. Distinct patterns representing each basic taste could be decoded above chance across several clusters within the middle and posterior insular bilaterally, despite a high degree of spatial variability across participants. Overall, valence decoding was weaker, and the resulting significant clusters showed generally low overlap with those obtained from taste-quality decoding. In agreement with prior reports, these results suggest that taste quality might be encoded in the insular cortex according to individual functional response patterns rather than to an anatomically consistent chemotopic arrangement. Albeit preliminary, this analysis extends this notion by proposing that taste quality and valence are represented by distinct insular cortical clusters.
This study aimed to provide a comprehensive multiobserver magnetic resonance imaging (MRI)-based assessment of olfactory bulb (OB) morphology, including volume, width, height, anterior-posterior diameter (APD), as well as olfactory sulcus (OS) depth, in normosmic adults. High-resolution MRI scans of 118 healthy participants (mean age 28.47 ± 8.20) were manually segmented by multiple observers. Interobserver reliability was generally acceptable, with OS depth and APD showing excellent agreement. Single-observer assessments were sufficient for group-level OB morphology, but caution was advised when interpreting individual cases. Besides, right OS depth and left height decreased with age in normosmic participants, and odor discrimination was positively associated with left OB width. People with deeper right OS depth had bigger right volume and longer APD. No correlations were found between olfactory function and OB morphological parameters. OS depth was consistently deeper on the right side, supporting hemispheric asymmetry. OB shape was most often oval (≈78%). Over 70% of the subjects showed left-right consistency in OB shape, but the Cohen's κ value indicated only slight (below moderate) agreement, suggesting that left-right agreement was limited. In conclusion, we presented a standardized multiobserver segmentation and measurement workflow that enabled reliable assessment of OB structure and OS depth, and offered a comprehensive characterization of OB and OS depth morphology in normosmia.
