'Sniffin' Sticks': Olfactory Performance Assessed by the Combined Testing of Odour Identification, Odor Discrimination and Olfactory Threshold

‘Sniffin’ Sticks' is a new test of nasal chemosensoryperformance based on pen-like odor dispensing devices. It comprisesthree tests of olfactory function, namely tests for odor threshold(n-butanol, testing by means of a single staircase), odor discrimination(15 pairs of odorants, triple forced choice) and odor identification(16 common odorants, multiple forced choice from four verbalitems per test odorant). After extensive preliminary investigationsthe tests were applied to a group of 104 healthy volunteers(52 female, 52 male, mean age 49.5 years, range 18–84years) in order to establish test-retest reliability and tocompare them with an established measure of olfactory performance(the Connecticut Chemosensory Clinical Research Center Test,CCCRC). Performance decreased with increasing age of the subjects(     

Concentration-dependent changes of perceived odor quality

In order to assess the dependence of perceived odor qualityon odorant concentration, we studied 21 subjects. For eightsubjects all possible pairs from a pool of six odorants at threedecimal dilutions were presented, and subjects were requestedto state whether members of the pair were qualitatively ‘similar’or ‘different’ It was found that while pairs withthe same odorant at identical concentrations were judged ‘similar’in >90% of the cases by all subjects, scores went down to10% ‘similar’ judgements in some cases when thesame odorant was presented at a 100-fold concentration difference.Large time-invariable differences were found among subjectsand among odorants. For the additional 13 subjects, all possiblepairs from a pool of four odorants at three decimal dilutionswere presented. Subjects were instructed to state whether membersof the pair were qualitatively ‘same’ or ‘different’,and were also requested to rank the degree of difference ona visual analogue scale. Results for this group were, in general,similar to the results of the former group of subjects and goodagreement between the two tasks was found. The results suggestthat variations in olfactory stimulus magnitude may be perceivedas quality differences, as previously shown for vision and audition.     

Construction of a Quantitative Three-dimensional Model for Odor Quality using Comparative Molecular Field Analysis (CoMFA)

A quantitative structure-activity relationship (QSAR) studyof odorants was performed taking an odor as an activity. Asan example, we took the ‘green odor of pyrazine derivatives’as an activity. Conformational analysis of the pyrazine derivativeswas performed, and conformers were selected using the longestside-length of a circumscribed box (LLCB) as a criterion. Comparativemolecular field analysis (CoMFA) was used to elucidate the three-dimensional(3D) structural features of the derivatives. As a result, itwas found that the steric and electrostatic features of thederivatives were correlated with human olfactory detection thresholdvalues. We constructed a quantitative 3D model using the graphicviews of CoMFA and partial structures of the derivatives. Theprediction of human olfactory detection threshold values ofother pyrazine derivatives with green odor was possible by usingthe 3D model. As another example, we took the ‘sweet odorof compounds with various structures’ as an activity.A quantitative 3D model for sweet odor was constructed in thesame manner. Analysing the structural features of odorants byCoMFA and constructing 3D models for several important odorqualities would help to (i) explain or predict human olfactorydetection threshold values of interesting odorants, (ii) designnew odorants by suggesting the steric and electrostatic requirements,and (iii) elucidate the mechanism of odorant-receptor interaction.Chem Senses 21: 201–210, 1996.     

New studies on odour discrimination in the frog's olfactory receptor cells. I. Experimental results

New experiments were performed within a systematic investigationof the discriminative properties of olfactory receptor cellsin the frog. Extracellular spike responses of receptor unitswere recorded during stimulation with 39 different odorants.Several general properties of the olfactory receptors, alreadydescribed, were confirmed. The overall selectivity was foundto be lower than in previous studies. Enantiomeric forms ofcitronellol and carvone were discriminated by several receptorcells, mainly in quantitative terms. In a series of eight cycloketones,each compound was the best stimulus for at least one receptorcell and some receptor cells had several ‘best stimuli’.Five odorants were delivered at two concentrations. All thereceptors responding to the lowest concentration also respondedto the highest one.     

Cognitive Processes in Odorant Mixture Assessment

‘Comparison of models of odor interaction’ by Cainand his colleagues (1995) is a turning point in assessment ofthe strengths of smell of mixtures of odorants. Their paperprovides the best empirical comparison to date of models of(olfactory) binary mixture intensities and combines this analysiswith a cogent critique of the whole tradition of mixture psychophysics.This commentary on their paper argues that their critique isnot radical enough. Chem. Senses 20: 639–643, 1995.     

Detection thresholds for an olfactory mixture and its three constituent compounds

Single sub-threshold odorants can, according to a few reports,become perceptible in concert. That is, they can exhibit mixtureadditivity. The present study measured thresholds for mixtureof 1-butanol, 2-pentanone, and n-butyl acetate, and for eachof these separately. ‘Complete’ additivity resulted,in that the threshold concentration of each compound in themixture (measured by gas chromatography) turned out to be one-thirdof each component separately. Earlier threshold studies alsoclaimed complete additivity and even hyper-additivity (synergism);in this regard they, like this study, differ from the more numerousstudies of suprathreshold mixtures, which yield imperfect additivity(hypo-additivity). Mixtures not only enhance sensitivity, butthey may also promote stability; intersubject variability wassmaller for the mixture than for the components. Subjects were20 young (18–26 years) and 20 elderly (69–91 years)persons, who gave two sets of thresholds on 2 days. Concordantwith earlier findings, the elderly's thresholds averaged higher(     

Protection of olfactory responses from inhibition by ethyl bromoacetate, diethylamine, and other chemically active odorants by certain esters and other compounds

Certain vaporous chemicals (chemically active odorants) arecapable of both stimulating olfactory responses and reactingwith receptors, ion channels, or receptor/ionophore macromoleculesto inhibit olfactory responses. We have studied the physiologicaleffects of several chemically active odorants using electrophysiologicaltechniques to record electroolfactogram (EOG) responses fromthe frog's olfactory mucosa. So far, the most studied agentsare ethyl bromoacetate (EBA), an alkylating agent, and diethylamine(DEA), a compound which is one of the strongest neutral organicbases. Certain odorants, or ‘protectants’, whenpresent before, during, and after exposure of the olfactorymucosa to either EBA or DEA have the property of maintainingolfactory responses which would otherwise be inhibited by exposureto the chemically active odorant alone. Protection from inhibitionby EBA is conferred by the presence of isoamyl acetate and afew closely-related esters, while protection from inhibitionby DEA is produced by the presence of p-dichlorobenzene. Protectionfrom inhibition by DEA is also achieved by lowering the pH ofthe olfactory mucosa through the simultaneous delivery of CO₂which produces carbonic acid. The mechanism of protection byesters and p-dichlorobenzene is unknown, but it seems likelythat these odorants somehow interfere with the access of thechemically active odorant to a site where it would normallyreact. ¹Present address: PSC Box 511, Peterson AFB, Colorado Springs,Colorado 80914, USA. ²Permanent address: Department of Chemistry, New Mexico Instituteof Mining and Technology, Socorro, New Mexico 87801, USA.     

Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction

Recent studies that have compared CT or MRI images of an individual's nasal anatomy and measures of their olfactory sensitivity have found a correlation between specific anatomical areas and performance on olfactory assessments. Using computational fluid dynamics (CFD) techniques, we have developed a method to quickly (相似文献   

Two molecular motility systems of the frog olfactory cilia

Intravital video microscopy was used to study the motility of frog (Rana temporaria) olfactory cilia exposed to various odorants—pentanol, camphor, cineole, and vanillin (first group); ammonia and hydrogen sulfide (second group)—and to the cell respiration inhibitors rotenone and malonate. It was demonstrated that the olfactory cilia had both the dynein-tubulin and actin-myosin molecular motility systems, the former providing unordered and the latter, ordered movements. The motility became ordered in response to exposure to odorants. The tested odorants belonging to different groups had different effects on the mitochondrial respiratory chain activity and the motility of olfactory cilia.     

Influence of stimulus intensity on odour discrimination by olfactory bulb neurons as compared with receptor cells

Previously reported electrophysiological responses recordedfrom individual neurons in the olfactory bulb of frogs stimulatedwith odorous compounds were further analyzed using statisticalmethods. Five of the odorants were delivered at two concentrations.The pattern of discrimination among these odorants was investigatedwith the aid of the Pearson's correlation test and Benzecri's‘analyse des correspondances’. Special attentionwas paid to the incidence of odour concentration on this discriminationpattern. The results were compared with those of a similar studyperformed on receptor cells in the same experimental conditions.The comparison indicated that the information processing inthe olfactory bulb seems to improve discrimination between chemicallydifferent stimuli, especially those poorly discriminated byreceptor cell responses, whereas it protects this discriminationagainst a massive influence of the intensity of the stimuli.     

New studies on odour discrimination in the frog's olfactory receptor cells. II. Mathematical analysis of electrophysiological responses

Revial et al. (1982) reported the experimental findings obtainedin cell units stimulated with two new sets of odorants. Thepresent paper deals with mathematical processing of these electrophysiologicaldata. The multidimensionality of the odour space was confirmed.Camphor, isoborneol and cineole appeared to represent a ‘camphorgroup’ markedly discriminated from other odorants. A‘terpenegroup’ including terpinene, dimethylstyrene, limoneneand cymene and related to menthane and menthene was observed.A series of 8 cycloketones was found to have a linear patternin the factorial planes and to be subdivided into three subsets.Cyclooctadecanone and cyclotetradecanone displayed correlationsand spatial relationships with musk ketone while cycloundecanone,cyclodecanone and especially cyclononanone were more relatedto the‘camphor group’. Separate processing of theunitary responses of 12 receptor cells recorded from a singlepreparation led to the building of a factorial space resemblingthat constructed with the full collection of data. The incidenceof odorant concentration on similarity evaluation is discussedon the basis of receptor responses to two different concentrationsof some of the odorants.     

Olfactory acuity after total laryngectomy

The olfactory acuity of 29 patients receiving laryngectomy was prospectively studied. The olfactory acuity was evaluated by Jet Stream Olfactometer (JSO) and Alinamin test preoperatively and at 3, 6 and 12 months postoperatively. The findings of nasal/olfactory mucosae were also observed by rigid endoscope. Based on the results of JSO, the averages of detection/recognition thresholds tended to increase 3 months postoperatively, then the averaged thresholds tended to decrease thereafter. There were significant differences between preoperative values and those 3 months after surgery, but there were no significant differences between preoperative values and these 6/12 months after surgery. Nasal respiratory mucosae observed 12 months after laryngectomy showed atrophic nasal mucosa in 11/14 patients. However, olfactory mucosae appeared normal in all of the patients observed. These results suggested that the function of the olfactory epithelium remained intact after laryngectomy.     

A computational study of odorant transport and deposition in the canine nasal cavity: implications for olfaction

Olfaction begins when an animal draws odorant-laden air into its nasal cavity by sniffing, thus transporting odorant molecules from the external environment to olfactory receptor neurons (ORNs) in the sensory region of the nose. In the dog and other macrosmatic mammals, ORNs are relegated to a recess in the rear of the nasal cavity that is comprised of a labyrinth of scroll-like airways. Evidence from recent studies suggests that nasal airflow patterns enhance olfactory sensitivity by efficiently delivering odorant molecules to the olfactory recess. Here, we simulate odorant transport and deposition during steady inspiration in an anatomically correct reconstructed model of the canine nasal cavity. Our simulations show that highly soluble odorants are deposited in the front of the olfactory recess along the dorsal meatus and nasal septum, whereas moderately soluble and insoluble odorants are more uniformly deposited throughout the entire olfactory recess. These results demonstrate that odorant deposition patterns correspond with the anatomical organization of ORNs in the olfactory recess. Specifically, ORNs that are sensitive to a particular class of odorants are located in regions where that class of odorants is deposited. The correlation of odorant deposition patterns with the anatomical organization of ORNs may partially explain macrosmia in the dog and other keen-scented species.     

ODOR DISCRIMINATION BY FROG OLFACTORY RECEPTORS

Single unit activity of olfactory receptors was recorded inthe frog. Seventy per cent of the receptors displayed a restingfrequency lower than 20 spikes min^–1. A 20 ways olfactometerwas designed to automatically stimulate the olfactory epitheliumwith 20 highly purified, simple odorants belonging to severalchemical series, each at a single supraliminal concentration.Twenty three cells failed to respond to any of the 20 stimuli.Following a total of 1160 stimulations delivered to 58 receptorcells, 241 activating and 59 inhibitory responses were recorded,leading to an overall selectivity of 25.8%. Twelve units wereexcited by only one of the 20 chemicals. The activating and inhibitory responses were submitted to mathematicalprocedures (calculation of the Pearson's ‘r’ correlationcoefficient, Benzecri's analysis of correspondences) in orderto determine similarities or proximities between odorants accordingto the response profiles of the receptors. The odour space builtfrom these data was clearly multidimensional. The five primaryaliphatic alcohols of the sample failed to exhibit any specialinter-relationship, except the propanolbutanol pair. Camphorwas quite unrelated to the other chemicals. Six odorants whichpossess in common the aromatic nucleus were found to be relatedby high correlation coefficients; they grouped themselves ina cluster in factor analysis diagrams. They are: benzene, naphthalene,anisole, acetophenone and the almond pair nitrobenzene-benzaldehyde.     

Odorant-induced kinetics of Ca<Superscript>2+</Superscript>, NADH,and oxidized flavoproteins in frog olfactory mucosa

A study was made of the odorant-induced changes in the fluorescence of the Ca²⁺-chlortetracycline-membrane complex, NADH, and oxidized flavoproteins in the frog olfactory epithelium. Cineole and vanillin induce faster changes than camphor and pentanol. The different kinetics of NADH and membrane calcium evoked by these odorants are attributed to the heterogeneity of the molecular mechanisms involved in olfactory signal transduction. By contrast, ammonia and β-mercaptoethanol permeate the olfactory cells and without second messengers inhibit the mitochondrial respiratory chain and suppress the motility of olfactory cilia.     

Kinetics of Ca2+, NADH, and oxidized flavoproteins in the frog olfactory lining under the effect of odorants

The kinetics of fluorescence of Ca(2+) - chlortertacyclin-cell membrane complex as well as of NADH and oxidized flavoproteins in receptor cells of the frog olfactory lining under the effect of odorants has been studied. Changes in the fluorescence of the olfactory lining upon stimulation by cineole and vanillin occurred more rapidly than under the effect of camphor and amyl alcohol. Differences in the kinetics of reactions of NADH and the Ca(2+)-CTC-CM complex to different odorants are apparently due to heterogeneity of molecular mechanisms associated with the involvement of different intracellular signal systems in the transduction of these odorants in the olfactory lining. In contrast to them, ammonia and beta3-mercaptoethanol penetrate into olfactory cells and inhibit the mitochondrial respiratory chain without the participation of second messengers. At the same time, the motor activity of olfactory cilia is depressed.     

Sniffing and spatiotemporal coding in olfaction

The act of sniffing increases the air velocity and changes the duration of airflow in the nose. It is not yet clear how these changes interact with the intrinsic timing within the olfactory bulb, but this is a matter of current research activity. An action of sniffing in generating a high velocity that alters the sorption of odorants onto the lining of the nasal cavity is expected from the established work on odorant properties and sorption in the frog nose. Recent work indicates that the receptor properties in the olfactory epithelium and olfactory bulb are correlated with the receptor gene expression zones. The responses in both the epithelium and the olfactory bulb are predictable to a considerable extent by the hydrophobicity of odorants. Furthermore, receptor expression in both rodent and salamander nose interacts with the shapes of the nasal cavity to place the receptor sensitivity to odorants in optimal places according to the aerodynamic properties of the nose.     

A STUDY OF OLFACTORY DISCRIMINATION IN THE RAT WITH THE AID OF A NEW ODOR DELIVERY TECHNIQUE

A technique for delivering odors at specific concentrationsand for precise periods into the nasal cavity of a freely movingrat is described. This is accomplished by linking the outletof an automatic micro-olfactometer to a cannula chronicallyimplanted into the nasal cavity of the rat. Details of the constructionand implantation of the cannula are given. Using this odor deliverytechnique rats were trained in a two-choice discrimination procedureto distinguish between the odors of benzaldehyde and benzonitrile(both are ‘almond like’), benzaldehyde and isobutylbutyrate(fruity), and benzonitrile-isobutylbutyrate. The rats foundthe olfactory properties of benzaldehyde and benzonitrile tobe similar, and each to be very different to the olfactory propertiesof isobutylbutyrate. It is proposed that the rat may use morethan a single olfactory property of each stimulus to discriminatebetween two odors. ^* This paper reports research undertaken at the School of BiologicalSciences, Macquarie University, and the CSIRO Division of FoodResearch.     

Taste- and odor-reactivity in elderly demented patients

Previous studies demonstrated that hedonically different chemical(taste or smell) stimuli induceinnate, inherited, differentialand distinct fixed reflectory motion features in the oral andfacial area. In the present study 20 elderly demented patients,suffering from ‘probable’ or ‘possible’Alzheimer's disease, and 20 normally functioning elderly subjectswere tested. The facial expressive behavioral reactions triggeredby a set of common gustatory and olfactory stimuli were videotaped.Both psychophysical and stimulus-dependent behavioral responseswere obtained from the control group, while for the dementedpatients only behavioral reactions were recorded. Results revealedthat: (i) severely demented elderly subjects displayed differentialand distinct orofacial responses indicating ‘acceptance’and ‘aversion’. These were found to be analogousto but less intense than those displayed by control age mates;(ii) the duration of responses induced by aversive tastes islonger than that triggered by pleasant or indifferent ones,for both groups; (iii) all gustatory and olfactory stimuli triggera longer lasting behavioral response in demented than in normalsubjects; and (iv) psychophysical and behavioral responses ofthe control subjects gave similar results for taste- and odor-hedonicsas well as for their intensity. This finding clearly indicatesthe validity of the alternative use of psychophysical and behavioraltesting procedures.