Dedicated odor-taste stimulation design for fMRI flavor studies.

BACKGROUND: Flavor is a mental representation that results from the brain's integration of at least odor and taste, and fMRI can highlight brain-related areas. However, delivering stimuli during fMRI can be challenging especially when administrating liquid stimuli in supine position. It remains unclear how and when odorants are released in the nose and how to improve odorant release. NEW METHOD: We used a proton transfer reaction mass spectrometer (PTR-MS) to monitor the in vivo release of odorants via the retronasal pathway during retronasal odor-taste stimulation in a supine position. We tested techniques to improve odorant release, including avoiding or delaying swallowing and velum open training (VOT). RESULTS: Odorant release was observed during retronasal stimulation, before swallowing, and in a supine position. VOT did not improve odorant release. Odorant release during stimulation had a latency more optimal for fitting with BOLD timing than after swallowing. COMPARISON WITH EXISTING METHOD(S): Previous in vivo measurements of odorant release under fMRI-like conditions showed that odorant release occurred only after swallowing. On the contrary, a second study found that aroma release could occur before swallowing, but participants were sitting. CONCLUSION: Our method shows optimal odorant release during the stimulation phase, meeting the criteria for high-quality brain imaging of flavor processing without swallowing-related motion artifacts. These findings provide an important advancement in understanding the mechanisms underlying flavor processing in the brain.

Using event-related potentials to study food-related cognition: An overview of methods and perspectives for future research.

Electroencephalography (EEG), and the measure of event-related potentials (ERPs) in particular, are useful methods to study the cognitive and cerebral mechanisms underlying the perception and processing of food cues. Further research on these aspects is necessary to better understand how cognitive functioning may influence food choices in different populations (e.g. obese individuals, individuals with eating disorders). To help researchers in designing future studies, this article provides an overview of the methods used in the current literature on ERPs and food-related cognition. Several methodological aspects are explored to outline interesting perspectives for future research, including discussions on the main experimental tasks used, the cognitive functions assessed (e.g. inhibitory control, attentional processing), the characteristics of the participants recruited (e.g. weight status, eating behaviors), and the stimuli selected (e.g. food pictures, odors). The issues generated by some of these methodological choices are discussed, and a few guidelines are provided.

Olfactory adaptation: recordings from the human olfactory epithelium.

PURPOSE: Olfactory adaptation is a peripheral (at the epithelium level) or a central (at the brain level) mechanism resulting from repeated or prolonged odorous exposure that can induce a perceptual decrease. The aim of this study was to assess whether a peripheral adaptation occurs when an odor is repeated ten times. Moreover, the specificity of the peripheral adaptation to the nature of the odorant was investigated. METHODS: Four odorants (eugenol, manzanate, ISO E Super and phenylethanol) were presented using precisely controlled air-dilution olfactometry. They differed in terms of their physicochemical properties. Electrophysiological recordings were made at the level of the olfactory mucosa, the so-called electro-olfactogram (EOG). Thirty-five right-handed participants were recruited. RESULTS: Sixty-nine percent of the participants presented at least one EOG, whatever the odor condition. The EOG amplitude did not significantly decrease over 10 repeated exposures to any odorant. The intensity ratings tended to decrease over stimulations for manzanate, PEA, and eugenol. No correlation was found between the mean EOG amplitudes and the mean intensity ratings. However, the presence of EOG amplitude decreases over stimulations for few subjects suggests that peripheral adaptation might exist. CONCLUSION: Overall, our results did not establish a clear peripheral adaptation measured with EOG but indicate the eventuality of such an effect.

Do Food Odors Differently Influence Cerebral Activity Depending on Weight Status? An Electroencephalography Study of Implicit Olfactory Priming Effects on the Processing of Food Pictures.

Attentional automatic processes and cerebral activity may differ between individuals with different weight statuses in the presence of food stimuli (e.g. odors, pictures). In the present study, we used an implicit olfactory priming paradigm to test the influence of non-attentively perceived food odors on the cerebral activity underlying the processing of food pictures, in normal-weight, overweight, and obese adults. A pear odor and a pound cake odor were used as primes, respectively priming sweet low-energy-density foods and high-energy-density foods. Event-related potentials were recorded while the participants passively watched pictures of sweet low and high-energy-density foods, under the two priming conditions plus an odorless control condition. The amplitude and latency of several peaks were measured (P100, N100, P200, N400). As a major result, we found that weight status influences the cerebral activity underlying the processing of food cues outside of consciousness, as early as the first detectable P100 peak.

Older and Young Adults Experience Similar Long-Term Olfactory Habituation.

Olfactory habituation corresponds to a decreased behavioral or perceptual response to an odor after a prolonged exposure to this odor. Our aim was to investigate whether long-term olfactory habituation and its recovery are similar in young (<35 years old) and older adults (>50). Fifty-seven participants were recruited for a 5-week longitudinal study. They were exposed to one of the two odors (manzanate alpha [MA], irone alpha [IA]) for 2 weeks at home. Olfactory detection thresholds for both odors were measured before and after exposure. Results showed that the two age groups behaved similarly. The long-term exposure to an odor led to a temporary increase of its detection threshold (lower sensitivity to the odor). IA thresholds were more sensitive to the duration of exposure with the odor than MA thresholds. One week after termination of exposure, participants fully recovered and even became more sensitive to both odors. No cross-habituation was found between the two odors. Our findings highlight that long-term habituation is specific to the odor exposed, behaves the same in young and older adults, and is fully reversible in both age groups after 1 week.

Odor-Induced Saltiness Enhancement: Insights Into The Brain Chronometry Of Flavor Perception.

Flavor perception results from the integration of at least odor and taste. Evidence for such integration is that odors can have taste properties (odor-induced taste). Most brain areas involved in flavor perception are high-level areas; however, primary gustatory and olfactory areas also show activations in response to a combination of odor and taste. While the regions involved in flavor perception are now quite well identified, the network's organization is not yet understood. Using a close to real salty soup model with electroencephalography brain recording, we evaluated whether odor-induced saltiness enhancement would result in differences of amplitude and/or latency in late cognitive P3 peak mostly and/or in P1 early sensory peak. Three target solutions were created from the same base of green-pea soup: i) with a "usual" salt concentration (PPS2), ii) with "reduced" salt (PPS1: -50%), and iii) with reduced salt and a "beef stock" odor (PPS1B). Sensory data showed that the beef odor produced saltiness enhancement in PPS1B in comparison to PPS1. As the main EEG result, the late cognitive P3 peak was delayed by 25 ms in the odor-added solution PPS1B compared to PPS1. The odor alone did not explain this peak amplitude and higher latency in the P3 peak. These results support the classical view that high-level integratory areas process odor-taste interactions with potential top-down effects on primary sensory regions.

Modelling analysis of centroid curves of olfactory habituation in humans.

Previously published experiments established the time-course of olfactory habituation in humans, and extracted 3 centroid curves from clustering analysis that reflected high, middle and low habituation. The aim of the current theoretical study was to further analyse these previous experimental data by developing a mathematical modelling analysis designed for fitting the 3 curves from a general equation. After adjusting equation parameters for each curve, fitting equation outcomes on experimental data yielded high correlation coefficients of 0.9997 - 0.9995 - 0.9962, respectively. A model-based interpretation of olfactory-habituation centroid curves is proposed suggesting that they result from the effect of 2 separate processes that act simultaneously. We suggest that the first process is unlikely related to the olfactory habituation itself, and, rather, is of unclear origin. The second process seems to play a major role in the degree of OH and cannot be assigned, a priori, to either peripheral or central adaptation, respectively.

The Presentation of Olfactory-Trigeminal Mixed Stimuli Increases the Response to Subsequent Olfactory Stimuli.

The aim of this study was to evaluate the effect of (1) the addition of trigeminal stimuli to an olfactory stimulus and (2) the congruence in the odorous mixture after repeated odor presentation. Twenty-five normosmic volunteers were enrolled and presented stimulation blocks, consisting of three habituation stimuli (H) (orange odor), one dishabituation (DH) (control condition, orange odor; congruent condition, orange odor + CO2; incongruent condition, orange odor + l-isopulegol), and one dishabituated stimulus (D) (orange odor). Olfactory event-related potentials were analyzed. Response amplitudes differed significantly in the incongruent condition (N1P2 between H3 and D; peak to peak N1P2 at electrode positions Cz, Fz, and Pz; response amplitudes between H3 and DH). The addition of CO2 modified the perception of orange odor, pronouncing a fruity note, whereas the addition of l-isopulegol as a DH pronounced the l-isopulegol note. This study provides evidence that incongruent trigeminal-olfactory stimulants increase the response to subsequent olfactory stimulus.

Learning to name smells increases activity in heteromodal semantic areas.

Semantic description of odors is a cognitively demanding task. Learning to name smells is, however, possible with training. This study set out to examine how improvement in olfactory semantic knowledge following training reorganizes the neural representation of smells. First, 19 nonexpert volunteers were trained for 3 days; they were exposed (i) to odorants presented without verbal labels (perceptual learning) and (ii) to other odorants paired with lexicosemantic labels (associative learning). Second, the same participants were tested in a brain imaging study (fMRI) measuring hemodynamic responses to learned odors presented in both the perceptual and associative learning conditions. The lexicosemantic training enhanced the ability to describe smells semantically. Neurally, this change was associated with enhanced activity in a set of heteromodal areas-including superior frontal gyrus-and parietal areas. These findings demonstrate that odor-name associative learning induces recruitment of brain areas involved in the integration and representation of semantic attributes of sensory events. They also offer new insights into the brain plasticity underlying the acquisition of olfactory expertise in lay people. Hum Brain Mapp 38:5958-5969, 2017. © 2017 Wiley Periodicals, Inc.

New determinants of olfactory habituation.

Habituation is a filter that optimizes the processing of information by our brain in all sensory modalities. It results in an unconscious reduced responsiveness to continuous or repetitive stimulation. In olfaction, the main question is whether habituation works the same way for any odorant or whether we habituate differently to each odorant? In particular, whether chemical, physical or perceptual cues can limit or increase habituation. To test this, the odour intensity of 32 odorants differing in physicochemical characteristics was rated by 58 participants continuously during 120s. Each odorant was delivered at a constant concentration. Results showed odorants differed significantly in habituation, highlighting the multifactoriality of habituation. Additionally habituation was predicted from 15 physico-chemical and perceptual characteristics of the odorants. The analysis highlighted the importance of trigeminality which is highly correlated to intensity and pleasantness. The vapour pressure, the molecular weight, the Odor Activity Value (OAV) and the number of double bonds mostly contributed to the modulation of habituation. Moreover, length of the carbon chain, number of conformers and hydrophobicity contributed to a lesser extent to the modulation of habituation. These results highlight new principles involved in the fundamental process of habituation, notably trigeminality and the physicochemical characteristics associated.

Grey matter changes of the pain matrix in patients with burning mouth syndrome.

Burning mouth syndrome (BMS) is characterized by a burning sensation in the mouth, usually in the absence of clinical and laboratory findings. Latest findings indicate that BMS could result from neuropathic trigeminal conditions. While many investigations have focused on the periphery, very few have examined possible central dysfunctions. To highlight changes of the central system of subjects with BMS, we analysed the grey matter concentration in 12 subjects using voxel-based morphometry. Data were compared with a control group (Ct). To better understand the brain mechanisms underlying BMS, the grey matter concentration of patients was also compared with those of dysgeusic patients (Dys). Dysgeusia is another oral dysfunction condition, characterized by a distorted sense of taste and accompanied by a reduced taste function. We found that a major part of the 'pain matrix' presented modifications of the grey matter concentration in subjects with BMS. Six regions out of eight were affected [anterior and posterior cingulate gyrus, lobules of the cerebellum, insula/frontal operculum, inferior temporal area, primary motor cortex, dorsolateral pre-frontal cortex (DLPFC)]. In the anterior cingulate gyrus, the lobules of the cerebellum, the inferior temporal lobe and the DLPFC, pain intensity correlated with grey matter concentration. Dys also presented changes in grey matter concentration but in different areas of the brain. Our results suggest that a deficiency in the control of pain could in part be a cause of BMS and that BMS and dysgeusia conditions are not linked to similar structural changes in the brain.

Experience shapes our odor perception but depends on the initial perceptual processing of the stimulus.

The questions of whether configural and elemental perceptions are competitive or exclusive perceptual processes and whether they rely on independent or dependent mechanisms are poorly understood. To examine these questions, we modified perceptual experience through preexposure to mixed or single odors and measured the resulting variation in the levels of configural and elemental perception of target odor mixtures. We used target mixtures that were spontaneously processed in a configural or an elemental manner. The AB binary mixture spontaneously involved the configural perception of a pineapple odor, whereas component A smelled like strawberry and component B smelled like caramel. The CD mixture produced the elemental perceptions of banana (C) and smoky (D) odors. Perceptual experience was manipulated through repeated exposure to either a mixture (AB or CD) or the components (A and B or C and D). The odor typicality rating data recorded after exposure revealed different influences of experience on odor mixtures and single-component perception, depending both on the type of exposure (components or mixture) and the mixture's initial perceptual property (configural or elemental). Although preexposure to A and B decreased the pineapple typicality of the configural AB mixture, preexposure to AB did not modify its odor quality. In contrast, preexposure to the CD elemental mixture induced a quality transfer between the components. These results emphasize the relative plasticity of odor mixture perception, which is prone to experience-induced modulations but depends on the stimulus's initial perceptual properties, suggesting that configural and elemental forms of odor mixture perception rely on rather independent processes.

Time-course of trigeminal versus olfactory stimulation: evidence from chemosensory evoked potentials.

Habituation of responses to chemosensory signals has been explored in many ways. Strong habituation and adaptation processes can be observed at the various levels of processing. For example, with repeated exposure, amplitudes of chemosensory event-related potentials (ERP) decrease over time. However, long-term habituation has not been investigated so far and investigations of differences in habituation between trigeminal and olfactory ERPs are very rare. The present study investigated habituation over a period of approximately 80 min for two olfactory and one trigeminal stimulus, respectively. Habituation was examined analyzing the N1 and P2 amplitudes and latencies of chemosensory ERPs and intensity ratings. It was shown that amplitudes of both components - and intensity ratings - decreased from the first to the last block. Concerning ERP latencies no effects of habituation were seen. Amplitudes of trigeminal ERPs diminished faster than amplitudes of olfactory ERPs, indicating that the habituation of trigeminal ERPs is stronger than habituation of olfactory ERPs. Amplitudes of trigeminal ERPs were generally higher than amplitudes of olfactory ERPs, as it has been shown in various studies before. The results reflect relatively selective central changes in response to chemosensory stimuli over time.

The perception of odor objects in everyday life: a review on the processing of odor mixtures.

Smelling monomolecular odors hardly ever occurs in everyday life, and the daily functioning of the sense of smell relies primarily on the processing of complex mixtures of volatiles that are present in the environment (e.g., emanating from food or conspecifics). Such processing allows for the instantaneous recognition and categorization of smells and also for the discrimination of odors among others to extract relevant information and to adapt efficiently in different contexts. The neurophysiological mechanisms underpinning this highly efficient analysis of complex mixtures of odorants is beginning to be unraveled and support the idea that olfaction, as vision and audition, relies on odor-objects encoding. This configural processing of odor mixtures, which is empirically subject to important applications in our societies (e.g., the art of perfumers, flavorists, and wine makers), has been scientifically studied only during the last decades. This processing depends on many individual factors, among which are the developmental stage, lifestyle, physiological and mood state, and cognitive skills; this processing also presents striking similarities between species. The present review gathers the recent findings, as observed in animals, healthy subjects, and/or individuals with affective disorders, supporting the perception of complex odor stimuli as odor objects. It also discusses peripheral to central processing, and cognitive and behavioral significance. Finally, this review highlights that the study of odor mixtures is an original window allowing for the investigation of daily olfaction and emphasizes the need for knowledge about the underlying biological processes, which appear to be crucial for our representation and adaptation to the chemical environment.

Is the age-related loss in olfactory sensitivity similar for light and heavy molecules?

The process of aging affects olfaction quite early and can lead to a major handicap. One may ask whether olfactory loss is general or if it affects some odors more specifically? We investigated whether an age-related increase in olfactory threshold could be more or less specific to heavy or light molecules, based on the idea that these odors would bind differently to olfactory receptors. One group of 30 older subjects (50-70 years) and one group of 30 young adults (18-30 years) were tested for their threshold to 4 odors. Two odorants were light molecules (<150 g/mol) and the 2 others were heavy molecules (>150 g/mol). Both sets contained a single molecule and a binary mixture. Older subjects performed worse than young adults in an odor identification task, confirming a decline in the olfactory function. As a major result, young adults were as sensitive to light and heavy molecules; on the contrary, older subjects were less sensitive to heavy molecules (single molecule and binary mixture). The results suggest that older people present a heterogeneous olfactory loss more specific to heavier molecules.

Decreased perception of bourgeonal may be linked to male idiopathic infertility.

Regarding the chemotaxis of sperms, new insights have been gained during the last 20 years. Olfactory receptors are expressed on the flagellar midpiece of human spermatogenic cells. One of them, OR1D2, is also expressed in the olfactory epithelium. This receptor has been suggested to play a role in sperm chemotaxis and thus in fertility. As OR1D2 is activated by bourgeonal, the aim of the study was to investigate whether patients with idiopathic infertility would exhibit a decreased olfactory sensitivity toward bourgeonal. Participants were 14 patients with idiopathic infertility and 23 controls (all young fathers). After having ascertained normosmia, odor thresholds and intensity ratings for the pleasant and flowery odors of bourgeonal, helional, and phenylethylalcohol were obtained. As a result, patients had specifically decreased intensity ratings for bourgeonal. It suggests that men with unexplained infertility tend to be less suprathreshold sensitive toward the odor of bourgeonal but not to that of other floral odors. It may be speculated that the decreased olfactory sensitivity relates to a decreased functionality of OR1D2, which in turn may be linked to idiopathic infertility.

Rabbit neonates and human adults perceive a blending 6-component odor mixture in a comparable manner.

Young and adult mammals are constantly exposed to chemically complex stimuli. The olfactory system allows for a dual processing of relevant information from the environment either as single odorants in mixtures (elemental perception) or as mixtures of odorants as a whole (configural perception). However, it seems that human adults have certain limits in elemental perception of odor mixtures, as suggested by their inability to identify each odorant in mixtures of more than 4 components. Here, we explored some of these limits by evaluating the perception of three 6-odorant mixtures in human adults and newborn rabbits. Using free-sorting tasks in humans, we investigated the configural or elemental perception of these mixtures, or of 5-component sub-mixtures, or of the 6-odorant mixtures with modified odorants' proportion. In rabbit pups, the perception of the same mixtures was evaluated by measuring the orocephalic sucking response to the mixtures or their components after conditioning to one of these stimuli. The results revealed that one mixture, previously shown to carry the specific odor of red cordial in humans, was indeed configurally processed in humans and in rabbits while the two other 6-component mixtures were not. Moreover, in both species, such configural perception was specific not only to the 6 odorants included in the mixture but also to their respective proportion. Interestingly, rabbit neonates also responded to each odorant after conditioning to the red cordial mixture, which demonstrates their ability to perceive elements in addition to configuration in this complex mixture. Taken together, the results provide new insights related to the processing of relatively complex odor mixtures in mammals and the inter-species conservation of certain perceptual mechanisms; the results also revealed some differences in the expression of these capacities between species putatively linked to developmental and ecological constraints.

Experience influences elemental and configural perception of certain binary odour mixtures in newborn rabbits.

Elemental and configural olfactory perception allows interaction with the environment from very early in life. To evaluate how newborn rabbits can extract and respond to information from the highly complex chemical surroundings, and how experience acts on this sensory, cognitive and behavioural capability, we ran a study in four steps including a total of eight experiments. We mainly used a binary AB mixture comprising ethyl isobutyrate (component A) and ethyl maltol (component B), previously shown as a bearer of blending properties; in rabbit pups (as in human adults), the mixture elicits a weak configural perception, i.e. the perception of a configural odour different from the odours of the components. First, a repeated exposure to one component of AB led to a more elemental perception of this mixture; conversely, a repeated exposure to AB facilitated its configural processing. Second, similar impact of experience did not appear with a non-blending AC mixture (ethyl isobutyrate-guaïacol). Third, repeated exposure to AB impacted not only the perception of AB, but also and in the same way the perception of the AC mixture sharing one component, and reciprocally. However, facilitation to perceive one mixture in one mode (configural/elemental) was not generalized to a mixture sharing no components with the experienced mixture [AB versus DE (damascenone and vanillin)]. Thus, experience contributes to the neonatal perception of odour mixtures and adds plasticity to the perceptual system. However, this impact remains dependent on the chemical composition of the mixtures.

A pheromone to behave, a pheromone to learn: the rabbit mammary pheromone.

Birth is part of a continuum and is a major developmental change. Newborns need to adapt rapidly to the environment in terms of physiology and behaviour, and ability to locate the maternal source of milk is vital. Mechanisms have evolved resulting in the emission of olfactory cues by the mother and the processing of these cues by the young. Here, we focus on some sensory, cognitive and behavioural strategies developed by the European rabbit (Oryctolagus cuniculus) that optimize the early development of offspring. In this species, chemosensory communication between the mother and young plays a critical role in eliciting adaptive neonatal responses. In particular, lactating females release a molecule, the mammary pheromone, which has several functional impacts. It triggers orocephalic responses involved in the quick localization of nipples and sucking. Moreover, this unconditioned signal promotes rapid appetitive learning of novel odorants, acting as a potent organizer of neonatal cognition. The mammary-pheromone-induced odour memory requires consolidation/reconsolidation processes to be maintained in the long term. Finally, as this mode of conditioning also promotes learning of mixtures of odorants, it supports investigations related to the capacity of neonatal olfaction to extract biological value from the complex environment.