Differential neural responses evoked by orthonasal versus retronasal odorant perception in humans

Odors perceived through the mouth (retronasally) as flavor are referred to the oral cavity, whereas odors perceived through the nose (orthonasally) are referred to the external world. We delivered vaporized odorants via the orthonasal and retronasal routes and measured brain response with fMRI. Comparison of retronasal versus orthonasal delivery produced preferential activity in the mouth area at the base of the central sulcus, possibly reflecting olfactory referral to the mouth, associated with retronasal olfaction. Routes of delivery produced differential activation in the insula/operculum, thalamus, hippocampus, amygdala, and caudolateral orbitofrontal cortex in orthonasal > retronasal and in the perigenual cingulate and medial orbitofrontal cortex in retronasal > orthonasal in response to chocolate, but not lavender, butanol, or farnesol, so that an interaction of route and odorant may be inferred. These findings demonstrate differential neural recruitment depending upon the route of odorant administration and suggest that its effect is influenced by whether an odorant represents a food.     

Retronasal perception of odors

Odors often produce different sensations when presented in front of the nose or intraorally, when eaten. It is a long-standing question whether these differences in sensations are due, for example, to the additional mechanical sensations elicited by the food in the mouth or additional odor release during mastication. To study this phenomenon in detail, a stimulation technique has been developed that allows controlled ortho- or retronasal presentation of odorous stimuli. Results from psychophysical, electrophysiological, and imaging studies suggest that there are clear differences in the perception of ortho- and retronasal stimuli. This 'duality of the sense of smell' is also observed in a clinical context where some patients exhibit good retronasal olfactory function with little or no orthonasal function left, and vice versa. The differences between ortho- and retronasal perception of odors are thought to be, at least partly, due to absorption of odors to the olfactory epithelium, which appears to differ in relation to the direction of the airflow across the olfactory epithelium.     

Color enhances orthonasal olfactory intensity and reduces retronasal olfactory intensity

The effect of color on orthonasal and retronasal odor intensities was investigated. When odorants were smelled orthonasally (i.e., through the nostrils), color enhanced odor intensity ratings, consistent with previous reports. However, when odorants were smelled retronasally (i.e., the odorous solution was put in the mouth), color reduced odor intensity ratings. These different effects of color on odor intensity (i.e., enhancement orthonasally and suppression retronasally) appear to be the result of route of olfactory stimulation rather than of any procedural artifact. This supports previous reports that retronasal and orthonasal odors are perceived differently.     

Orthonasal and Retronasal Odorant Identification Based upon Vapor Phase Input from Common Substances

Subjects were trained to identify by assigned number commonsubstances presented as vapor phase stimuli via an orthonasalor a retronasal route. Following training, odorant identificationlearning was evaluated by measuring ability to correctly identifyto a criterion. Those who met the criterion were then testedfirst with the stimuli presented to the nares that differedin location from the nares used in training, and second to thenares that corresponded in location to the nares used in training.It was found that, under conditions of natural retronasal breathing,orthonasally trained subjects made correct identifications on{small tilde}80% of the trials upon retronasal testing, butfor the following orthonasal testing identifications were significantlymore frequent, approaching 100% correct. After subsequent retronasaltraining, the same subjects' orthonasal identifications remainedsignificantly higher, although identifications improved to {smalltilde}92% correct on retronasal trials. Other subjects wereinstructed in a breathing technique designed to enhance retronasalstimulation. After orthonasal training, retronasal testing ofthese subjects still gave significantly fewer correct identificationsthan orthonasal testing, notwithstanding the modified retronasalbreathing, but after subsequent retronasal training correctidentifications by these subjects no longer differed significantlybetween orthonasal and retronasal testing. Efficacy of modifiedretronasal breathing was confirmed in two subsequent experiments.The observed substantial positive transfers between retronasaland orthonasal odorant identification training and testing locidemonstrate that these odorant pathways do not subserve completelyindependent olfactory systems, while the less accurate identificationsvia the retronasal route, unless instruction in retronasal breathingwas given, suggest a difference in the efficiency with whichodorants are normally delivered to the olfactory mucosa. Chem.Senses 21: 529–543, 1996.     

Superior Orthonasal but Not Retronasal Olfactory Skills in Congenital Blindness

Sight is undoubtedly important for finding and appreciating food, and cooking. Blind individuals are strongly impaired in finding food, limiting the variety of flavours they are exposed to. We have shown before that compared to sighted controls, congenitally blind individuals have enhanced olfactory but reduced taste perception. In this study we tested the hypothesis that congenitally blind subjects have enhanced orthonasal but not retronasal olfactory skills. Twelve congenitally blind and 14 sighted control subjects, matched in age, gender and body mass index, were asked to identify odours using grocery-available food powders. Results showed that blind subjects were significantly faster and tended to be better at identifying odours presented orthonasally. This was not the case when odorants were presented retronasally. We also found a significant group x route interaction, showing that although both groups performed better for retronasally compared to orthonasally presented odours, this gain was less pronounced for blind subjects. Finally, our data revealed that blind subjects were more familiar with the orthonasal odorants and used the retronasal odorants less often for cooking than their sighted counterparts. These results confirm that orthonasal but not retronasal olfactory perception is enhanced in congenital blindness, a result that is concordant with the reduced food variety exposure in this group.     

fMRI activation in response to odorants orally delivered in aqueous solutions

During food intake flavor perception results from simultaneous stimulation of the gustatory, olfactory and trigeminal systems. Olfactory stimulation occurs mainly through the retronasal pathway and the resulting perception is often interpreted as a taste perception, thus leading to the well-known sensory confusion between taste and olfaction. The present experiment was designed to study, with functional magnetic resonance imaging (fMRI), the cortical representation of olfactory perception in humans in response to retronasal stimulation by odorants delivered in aqueous solution. Psychophysical evaluation confirmed that the stimuli acted as pure olfactory stimuli through the retronasal pathway and did not present any taste component. Results showed activation in all brain regions previously described with neuroimaging techniques using olfactory stimulation with an odorized air flow. Piriform and orbitofrontal cortex were found activated as well as the hippocampal region, the amygdala, the insular lobe, the cingulate gyrus and the cerebellum. These results demonstrate the feasibility of efficiently stimulating the olfactory system in an fMRI scanner through the retronasal pathway with liquids delivered to the oral cavity. The presentation of olfactory stimuli in liquids to the mouth is a realistic model for the study of food-related flavor perception. This stimulation protocol furthermore allows presenting taste and olfactory stimuli separately or combined, thus allowing for direct comparisons between single modality representation, taste or olfaction, and representation of multi-modality mixtures.     

Direct Behavioral and Neurophysiological Evidence for Retronasal Olfaction in Mice

The neuroscience of flavor perception is hence becoming increasingly important to understand food flavor perception that guides food selection, ingestion and appreciation. We recently provided evidence that rats can use the retronasal mode of olfaction, an essential element of human flavor perception. We showed that in rats, like humans, odors can acquire a taste. We and others also defined how the input of the olfactory bulb (OB) -not functionally imageable in humans- codes retronasal smell in anesthetized rat. The powerful awake transgenic mouse, however, would be a valuable additional model in the study of flavor neuroscience. We used a go/no-go behavioral task to test the mouse''s ability to detect and discriminate the retronasal odor amyl acetate. In this paradigm a tasteless aqueous odor solution was licked by water-restricted head-fixed mice from a lick spout. Orthonasal contamination was avoided. The retronasal odor was successfully discriminated by mice against pure distilled water in a concentration-dependent manner. Bulbectomy removed the mice''s ability to discriminate the retronasal odor but not tastants. The OB showed robust optical calcium responses to retronasal odorants in these awake mice. These results suggest that mice, like rats, are capable of smelling retronasally. This direct neuro-behavioral evidence establishes the mouse as a useful additional animal model for flavor research.     

Mechanical obstruction of the olfactory cleft reveals differences between orthonasal and retronasal olfactory functions

Following up on recent observations in patients with nasal polyposis (NP), the present study aimed to investigate whether a mechanical obstruction of the anterior olfactory cleft (OC) would produce differential effects on orthonasal and retronasal olfactory functions. To this end, we studied 33 healthy subjects in a randomized trial. Sponges with high content of saline were either placed in the OC or on the respiratory epithelium, such that this was blinded to both subject and observer. The results indicated that orthonasal (P = 0.04) but not retronasal (P = 0.15) olfactory identification ability was lower when the OC was blocked. This confirms the idea that differences between orthonasal and retronasal olfactory functions, as observed in NP patients, are, at least to some degree, due to mechanical obstruction of the anterior portion of the OC. The present data also suggest that mechanical obstruction is a means to induce reversible hyposmia void of side effects which can be performed in a blinded fashion. This might become a valuable model of hyposmia for future investigations.     

Multiple routes of chemosensitivity to free fatty acids in humans

Selected free fatty acids (FFAs) are documented effective somatosensory and olfactory stimuli whereas gustatory effects are less well established. This study examined orthonasal olfactory, retronasal olfactory, nasal irritancy, oral irritancy, gustatory, and multimodal threshold sensitivity to linoleic, oleic, and stearic acids. Sensitivity to oxidized linoleic acid was also determined. Detection thresholds were obtained using a three-alternative, forced-choice, ascending concentration presentation procedure. Participants included 22 healthy, physically fit adults sensitive to 6-n-propylthiouracil. Measurable thresholds were obtained for all FFAs tested and in 96% of the trials. Ceiling effects were observed in the remaining trials. Greater sensitivity was observed for multimodal stimulation and lower sensitivity for retronasal stimulation. There were no statistically significant correlations for linoleic acid thresholds between different modalities, suggesting that each route of stimulation contributes independently to fat perception. In summary, 18-carbon FFAs of varying saturation are detected by multiple sensory systems in humans.     

The role of congruency in retronasal odor referral to the mouth

Referral of retronasal odors to the mouth is a fundamental phenomenon of flavor perception. A previous study from this laboratory provided evidence that, contrary to prior speculation, taste rather than touch was the primary factor in retronasal odor referral. The present study further investigated this question by studying the role of congruency between taste and odor on retronasal odor referral under conditions that mimicked natural food consumption. Subjects performed odor localization tasks after sampling gelatin stimuli that contained various congruent and incongruent tastes-odor combinations. The results showed that when a congruent taste was added, referral to the oral cavity and tongue were significantly enhanced. In addition, the data also indicate that the degree of congruency between taste and odor may modulate the degree of odor referral to the mouth. These findings suggest that odor referral is maximized when congruent flavor dimensions are combined to trigger perceptual "flavor objects" that represent known or potential foods. The results are discussed in terms of the factors that play a role in the retronasal odor referral as well as the potential neural mechanisms that may underlie it.     

Enhancement of retronasal odors by taste

Psychophysical studies of interactions between retronasal olfaction and taste have focused most often on the enhancement of tastes by odors, which has been attributed primarily to a response bias (i.e., halo dumping). Based upon preliminary evidence that retronasal odors could also be enhanced by taste, the present study measured both forms of enhancement using appropriate response categories. In the first experiment, subjects rated taste ("sweet," "sour," "salty," and "bitter") and odor ("other") intensity for aqueous samples of 3 tastants (sucrose, NaCl, and citric acid) and 3 odorants (vanillin, citral, and furaneol), both alone and in taste-odor mixtures. The results showed that sucrose, but not the other taste stimuli, significantly increased the perceived intensity of all 3 odors. Enhancement of tastes by odors was inconsistent and generally weaker than enhancement of odors by sucrose. A second experiment used a flavored beverage and a custard dessert to test whether the findings from the first experiment would hold for the perception of actual foods. Adding sucrose significantly enhanced the intensity of "cherry" and "vanilla" flavors, whereas adding vanillin did not significantly enhance the intensity of sweetness. It is proposed that enhancement of retronasal odors by a sweet stimulus results from an adaptive sensory mechanism that serves to increase the salience of the flavor of nutritive foods.     

Synergy and masking in odor mixtures: an electrophysiological study of orthonasal vs. retronasal perception

Perceptual interactions in a model of wine woody-fruity binary mixtures were previously reported in a psychophysical study performed through orthonasal stimulation only. However, recent studies suggested that the perception of food-like and nonfood-like odors may depend on the route of stimulation. The aim of the present study was two-fold: first to examine the neural correlates of perceptual interactions using electroencephalogram (EEG)-derived event-related potentials (ERPs) and second to test the influence of the stimulation route on quality perception. Therefore, we designed an experiment with 30 subjects to study perceptual interactions in woody-fruity mixtures and compared ortho- vs. retronasal stimulation sites on perceived odor quality and ERPs. The results revealed synergy or masking of the fruity component, depending on the woody component level. Synergy was supported by larger N1 amplitude of the ERP. Furthermore, mixtures including a medium level of the woody odor elicited a strong increase of P2 amplitude only retronasally. This study evidenced for the first time electrophysiological correlates of both perceptual synergy and masking on the early component of the ERPs and confirmed that retro- vs. orthonasal stimulation route induces different neural processes that are reflected in the late component of the ERP.     

Differences in olfactory bulb mitral cell spiking with ortho- and retronasal stimulation revealed by data-driven models

The majority of olfaction studies focus on orthonasal stimulation where odors enter via the front nasal cavity, while retronasal olfaction, where odors enter the rear of the nasal cavity during feeding, is understudied. The coding of retronasal odors via coordinated spiking of neurons in the olfactory bulb (OB) is largely unknown despite evidence that higher level processing is different than orthonasal. To this end, we use multi-electrode array in vivo recordings of rat OB mitral cells (MC) in response to a food odor with both modes of stimulation, and find significant differences in evoked firing rates and spike count covariances (i.e., noise correlations). Differences in spiking activity often have implications for sensory coding, thus we develop a single-compartment biophysical OB model that is able to reproduce key properties of important OB cell types. Prior experiments in olfactory receptor neurons (ORN) showed retro stimulation yields slower and spatially smaller ORN inputs than with ortho, yet whether this is consequential for OB activity remains unknown. Indeed with these specifications for ORN inputs, our OB model captures the salient trends in our OB data. We also analyze how first and second order ORN input statistics dynamically transfer to MC spiking statistics with a phenomenological linear-nonlinear filter model, and find that retro inputs result in larger linear filters than ortho inputs. Finally, our models show that the temporal profile of ORN is crucial for capturing our data and is thus a distinguishing feature between ortho and retro stimulation, even at the OB. Using data-driven modeling, we detail how ORN inputs result in differences in OB dynamics and MC spiking statistics. These differences may ultimately shape how ortho and retro odors are coded.     

Temporal synchrony and integration of sub-threshold taste and smell signals

The importance of stimulus timing and location on the perceptual integration of taste and odour was studied based on a sub-threshold methodology. From a panel of 16 people, 12 showed the integration effect previously reported while 4 showed no effect. The experiment was repeated using retronasal and orthonasal delivery of the odour and with tastant present or absent in the mouth. Integration of taste and odour only occurred when both stimuli were present at the same time. Retro- or orthonasal presentation both produced integration providing that tastant delivery was synchronous but the threshold values for the two presentation methods were different. The relevance of these findings to flavour perception under realistic conditions is considered.     

Potential mechanisms of retronasal odor referral to the mouth

The current study took a first step toward elucidating the sensory input that drives retronasal odor referral to the mouth. In 2 experiments, subjects performed odor localization tasks under various oral-nasal stimulation conditions that allowed us to assess the effects of direction of airflow, taste, and tactile stimulation on retronasal odor referral. Subjects reported the locations of perceived odors when food odorants were inhaled through the mouth alone or in the presence of water or various tastants in the mouth. The results indicated that when perceived alone, vanilla and soy sauce odor were localized 54.7%: 26.4%: 18.9% and 60.0%: 21.7%: 18.3% in the nose, oral cavity, and on the tongue, respectively. The localization of odors alone was not significantly different from when water was presented simultaneously in the mouth, indicating that tactile stimulation itself is not sufficient to enhance odor referral. However, the presence of sucrose, but not other tastes, significantly increased localization of vanilla to the tongue. Likewise, only NaCl significantly augmented referral of soy sauce odor to the tongue. These data indicate that referral of retronasal odors to the mouth can occur in the absence of a either taste or touch but that referral to the tongue depends strongly on the presence of a congruent taste.     

Food perception with age and its relationship to pleasantness

Differences between elderly subjects (n = 46, 61-86 years) and young subjects (n = 36, 18-25 years) in food perception and food liking were investigated. Intensity and liking ratings were assessed for custard dessert, in which flavor enrichment, textural change, and irritant addition were incorporated as strategies to compensate for sensory losses with increasing age. The sensory acuity (taste, olfaction, irritation, chewing efficiency) of both young and elderly subjects was measured with the help of different sensitivity tests. The elderly perceived the custards differently from the young, mainly as less intense in flavor (cherry/vanilla) and less intense in creaminess/swallowing effort. Several of the observed interaction effects were different for the elderly and the young. The majority of these differences manifested as lower intensity slopes for the elderly. Losses in sensitivity to taste and to olfactory and trigeminal stimuli as well as a reduced chewing efficiency were observed on average for the elderly compared with the young. Furthermore, subgroups of the elderly were observed in which the compensatory strategies flavor enrichment, textural change, and irritant addition led to an increase in food liking. However, these subgroups did not differ in their sensory acuity. The present study does not support the assumption that age-associated changes in food perception-caused by losses in sensory acuity-inevitably reduce the food liking of the elderly.     

Retronasal but not oral-cavity-only identification of "purely olfactory" odorants

Identifications of 5 odorants selected to be nontrigeminal stimuli were compared using retronasal and oral-cavity-only (OCO) air-phase presentations, with OCO produced by both exhalation through the mouth and a nose clip that closed the nostrils. Nine identifiers were available on each trial; 1 or 2 were correct for each odorant. Correct retronasal identifications were more common than OCO identifications and exceeded chance across subjects and for each subject; OCO correct identifications did not exceed chance. Retronasal reaction times were briefer than OCO reaction times. Correct retronasal identifications for vanillin, octanoic acid, phenylethyl alcohol, coumarin, and octane were 88%, 73%, 87%, 70%, and 85%, respectively; correct OCO identifications were, respectively, 10%, 12%, 18%, 35%, and 33%. Identifiers selected for retronasally presented odorants differed from those for other retronasally presented odorants, but identifiers for OCO-presented odorants did not differ between odorants. Overall, the retronasal identifications of nontrigeminal odorants both depended upon the odorant that was presented and corresponded to previous reported orthonasal identifications. In contrast, the OCO identifications, characterized by low percentages of correct identifications and an absence of differences between odorants in selected identifiers, suggested that OCO responses to nontrigeminal, purely olfactory odorants lack sufficient sensory information for either correct or differential identification.     

Investigation of breathing parameters during odor perception and olfactory imagery

Compared with visual and auditory imagery, little is known aboutolfactory imagery. There is evidence that respiration may bealtered by both olfactory perception and olfactory imagery.In order to investigate this relationship, breathing parameters(respiratory minute volume, respiratory amplitude, and breathingrate) in human subjects during olfactory perception and olfactoryimagery were investigated. Fifty-six subjects having normalolfactory function were tested. Nasal respiration was measuredusing a respiratory pressure sensor. Using an experimental blockdesign, we alternately presented odors or asked the subjectsto imagine a given smell. Four different pleasant odors wereused: banana, rose, coffee, and lemon odor. We detected a significantincrease in respiratory minute volume between olfactory perceptionand the baseline condition as well as between olfactory imageryand baseline condition. Additionally we found significant differencesin the respiratory amplitude between imagery and baseline conditionand between odor and imagery condition. Differences in the breathingrate between olfactory perception, olfactory imagery, and baselinewere not statistically significant. We conclude from our resultsthat olfactory perception and olfactory imagery both have effectson the human respiratory profile and that these effects arebased on a common underlying mechanism.     

Variables affecting denture satisfaction in Israeli elderly:a one year follow-up

The purpose of this study was to investigate patient satisfaction with complete dentures after one year of use and several potential mitigating factors in Israeli elderly. Eighty–four patients who were 54 years of age or older and who were rehabilitated with complete dentures were recalled for examination 12-15 months later; 84.5% (n=70) were interviewed and reexamined by calibrated examiners who judged all prostheses to be clinically acceptable. The mean age of participants was 71.90 years and two-thirds were females. Over 73 % reported that they wore their dentures “always.” Nearly 79% indicated that they were pleased with their denture appearance. Difficulties were reported by 28.2%, while 46.5% reported difficulties with chewing. Chewing problems were significantly related to swallowing problems (P<.001); food enjoyment “as much now as you did five years ago” (P<.001); difficulties speaking (P<.00105) and “having sores under your dentures” (P<.00101) which affected 28.2% of the survey group. Married elderly expressed higher satisfaction with denture comfort as compared to “single” patients, and patients suffering from any systemic chronic diseases were more dissatisfied with appearance. A summary satisfaction scale of 7 items was constructed (Cronbach alpha reliability 0.6834) and logistic regression performed to identify key model variables for overall satisfaction. Stat sign findings included: 1) immigration year; 2) neurological or psychological disorder; and 3) age. The model correctly classified 92.75%. Findings suggest that a variety of factors may influence denture satisfaction. Gathering detailed information by means of a questionnaire before new denture fabrication may be an important tool for the dentist in predicting and consequently enhancing patient satisfaction with complete dentures.     

Sensory detection of food odour in relation to dental status,gender and age

The aim of this study was to investigate to what extent declining odour perception can be ascribed to dental status and oral hygiene habits, taking into account gender and age. Apparently healthy adults (n=182), ranging from 53 to 93 years (mean age=68.4) were tested. Information about oral hygiene habits (brushing teeth and cleaning dentures) and dental status was obtained by questionnaires. A validated objective procedure was used to measure sensory detection thresholds for isoamylacetate by an ascending method of limits. A significant negative correlation of odour perception with age was shown by the edentulous subjects which might reflect their wider age spread with many subjects over age 75. The evaluation of odour perception as a function of dental status shows no significant difference in odour perception between persons partial denture wearers, with natural teeth only or complete dentures. However, a tendency for lower odour perception was observed among male partial denture wearers, especially those reporting less frequent oral hygiene, which justifies further more detailed study.