Beneficial effects of prolonged 2-phenylethyl alcohol inhalation on chronic distress-induced anxio-depressive-like phenotype in female mice.

Chronic distress-induced hypothalamic-pituitary-adrenal axis deregulations have been associated with the development of neuropsychiatric disorders such as anxiety and depression. Currently available drugs treating such pathological conditions have limited efficacy and diverse side effects, revealing the need of new safer strategies. Aromatic plant-based compounds are largely used in herbal medicine due to their therapeutic properties on mood, physiology, and general well-being. The purpose of this study was to investigate the effects of 2-phenylethyl alcohol (PEA), one of the pharmacologically active constituents of rose essential oil, on chronic corticosterone (CORT)-induced behavioral and neurobiological changes in female mice. Animals followed a prolonged PEA inhalation exposure (30 min per day) for 15 consecutive days prior to behavioral evaluation with open-field, forced swim and novelty-suppressed feeding tests. CORT treatment induced an anxio-depressive-like phenotype, evidenced by a reduced locomotor activity in the open-field, and an increased latency to feed in the novelty-suppressed feeding paradigms. To elucidate the neural correlates of our behavioral results, immunohistochemistry was further performed to provide a global map of neural activity based on cerebral cFos expression. The altered feeding behavior was accompanied by a significant decrease in the number of cFos-positive cells in the olfactory bulb, and altered functional brain connectivity as shown by cross-correlation-based network analysis. CORT-induced behavioral and neurobiological alterations were reversed by prolonged PEA inhalation, suggesting a therapeutic action that allows regulating the activity of neural circuits involved in sensory, emotional and feeding behaviors. These findings might contribute to better understand the therapeutic potential of PEA on anxio-depressive symptoms.

The Fate of Transplanted Olfactory Progenitors Is Conditioned by the Cell Phenotypes of the Receiver Brain Tissue in Cocultures.

Among the numerous candidates for cell therapy of the central nervous system (CNS), olfactory progenitors (OPs) represent an interesting alternative because they are free of ethical concerns, are easy to collect, and allow autologous transplantation. In the present study, we focused on the optimization of neuron production and maturation. It is known that plated OPs respond to various trophic factors, and we also showed that the use of Nerve Growth Factor (NGF) allowed switching from a 60/40 neuron/glia ratio to an 80/20 one. Nevertheless, in order to focus on the integration of OPs in mature neural circuits, we cocultured OPs in primary cultures obtained from the cortex and hippocampus of newborn mice. When dissociated OPs were plated, they differentiated into both glial and neuronal phenotypes, but we obtained a 1.5-fold higher viability in cortex/OP cocultures than in hippocampus/OP ones. The fate of OPs in cocultures was characterized with different markers such as BrdU, Map-2, and Synapsin, indicating a healthy integration. These results suggest that the integration of transplanted OPs might by affected by trophic factors and the environmental conditions/cell phenotypes of the host tissue. Thus, a model of coculture could provide useful information on key cell events for the use of progenitors in cell therapy.

Fatty Acid Lingual Application Activates Gustatory and Reward Brain Circuits in the Mouse.

The origin of spontaneous preference for dietary lipids in humans and rodents is debated, though recent compelling evidence has shown the existence of fat taste that might be considered a sixth taste quality. We investigated the implication of gustatory and reward brain circuits, triggered by linoleic acid (LA), a long-chain fatty acid. The LA was applied onto the circumvallate papillae for 30 min in conscious C57BL/6J mice, and neuronal activation was assessed using c-Fos immunohistochemistry. By using real-time reverse transcription polymerase chain reaction (RT-qPCR), we also studied the expression of mRNA encoding brain-derived neurotrophic factor (BDNF), Zif-268, and Glut-1 in some brain areas of these animals. LA induced a significant increase in c-Fos expression in the nucleus of solitary tract (NST), parabrachial nucleus (PBN), and ventroposterior medialis parvocellularis (VPMPC) of the thalamus, which are the regions known to be activated by gustatory signals. LA also triggered c-Fos expression in the central amygdala and ventral tegmental area (VTA), involved in food reward, in conjunction with emotional traits. Interestingly, we noticed a high expression of BDNF, Zif-268, and Glut-1 mRNA in the arcuate nucleus (Arc) and hippocampus (Hipp), where neuronal activation leads to memory formation. Our study demonstrates that oral lipid taste perception might trigger the activation of canonical gustatory and reward pathways.

Assessment of Olfactory Perception in Individuals with Motion Sickness.

BACKGROUND: Individuals who experience motion sickness (MS) frequently mention the presence of smells in the environment as a factor favoring the occurrence of MS symptoms. The aim of the present work was to compare olfactory function in MS sensitive (MS+) and insensitive (MS-) subjects. METHODS: Olfactory testing included determination of odor detection thresholds, subjective evaluation of the quality (intensity, hedonicity, and familiarity) of three different odorants (limonene, isovaleric acid, and petrol) as well as measures of skin conductance responses to these three odorants. RESULTS: Results showed no difference in olfactory sensitivity between MS+ and MS- subjects. However, findings of both subjective (odor quality self-rating) and objective (psychophysiological responses) measures did reveal that the affective response to petrol odor was significantly different in MS+ and in MS- subjects. Indeed, on a scale from 0 (unpleasant) to 10 (pleasant) MS+ subjects rated petrol odor as more unpleasant (mean = 2.52) than MS- subjects (mean = 4.15) and rise-time of skin conductance responses to petrol odor was significantly longer in MS+ (mean = 5.98 s) compared to MS- subjects (mean = 3.22 s). DISCUSSION: Our study delves further into the knowledge of the relationship between motion sickness and olfaction by demonstrating a modified olfactory perception in motion sickness sensitive subjects at both the psychophysical and psychophysiological levels.Jacquot L, Millot J-L, Paillard AC. Assessment of olfactory perception in individuals with motion sickness. Aerosp Med Hum Perform. 2018; 89(5):428-433.

Cerebral bases of emotion regulation toward odours: A first approach.

Emotion regulation is defined as an important mechanism for human adaptation. fMRI studies have recently highlighted its neural bases but most research uses visual stimulation to induce emotion, none of them using odorant stimulations. Nevertheless, olfaction is intimately linked to emotional processes, sharing some same neural bases and thus constitutes a valuable emotion-inducer in experimental conditions. The present study aims to determine the cerebral areas which might be involved in down-regulation, using pleasant and unpleasant odours as emotion-inducers. Eighteen subjects were scanned during 2 sequences of 12 stimulations, each with either a pleasant or an unpleasant odour. For one sequence, subjects were instructed to naturally experience their emotion induced by odour inhalation and for the other one, to decrease the intensity of their emotion. Consistent with previous work using emotion-inducers, emotion regulation resulted in higher activations of the dorsolateral prefrontal cortex and the anterior insula, but in lower activation of the amygdala. However, some areas (the posterior cerebellum and the orbitofrontal cortex) are less activated during regulation compared to maintain and thus appear to be specific to odorant stimulations. Finally the hedonic valence of the odour determines activations in different brain areas such as the supplementary motor area and the posterior cingulum. Thus, this study suggests abilities to regulate emotion in response to odours, involving brain areas usually described in the literature for other emotional stimuli, but also specific areas depending partly of the hedonic valence of the odour.

The Influence of Odors on Time Perception.

The effect of an olfactory stimulation on the perception of time was investigated through two different experiments based on temporal bisection tasks. In experiment 1, the durations to be classified as either short or long were centered on 400 ms while in Experiment 2 there were centered on 2000 ms. The participants were different in the two experiments (36 subjects in each one). In each experiment, half of the subjects learnt the anchor durations when smelling an unpleasant odor (decanoic acid) and the other half when smelling no odor. After the learning phase, both groups were tested with and without odor. The results showed opposite effects depending on the duration range. The subjects underestimated the time in the presence of the unpleasant odor in the short duration range while they overestimated it in the long duration range. The results have been discussed in the framework of the pacemaker-counter clock model and a potential emotional effect induced by the odor on the subjective time perception has also been considered.

Pulse Width Modulation Applied to Olfactory Stimulation for Intensity Tuning.

For most olfactometers described in the literature, adjusting olfactory stimulation intensity involves modifying the dilution of the odorant in a neutral solution (water, mineral, oil, etc.), the dilution of the odorant air in neutral airflow, or the surface of the odorant in contact with airflow. But, for most of these above-mentioned devices, manual intervention is necessary for adjusting concentration. We present in this article a method of controlling odorant concentration via a computer which can be implemented on even the most dynamic olfactometers. We used Pulse Width Modulation (PWM), a technique commonly used in electronic or electrical engineering, and we have applied it to odor delivery. PWM, when applied to odor delivery, comprises an alternative presentation of odorant air and clean air at a high frequency. The cycle period (odor presentation and rest) is 200 ms. In order to modify odorant concentration, the ratio between the odorant period and clean air presentation during a cycle is modified. This ratio is named duty cycle. Gas chromatography measurements show that this method offers a range of mixing factors from 33% to 100% (continuous presentation of odor). Proof of principle is provided via a psychophysical experiment. Three odors (isoamyl acetate, butanol and pyridine) were presented to twenty subjects. Each odor was delivered three times with five values of duty cycles. After each stimulation, the subjects were asked to estimate the intensity of the stimulus on a 10 point scale, ranging from 0 (undetectable) to 9 (very strong). Results show a main effect of the duty cycles on the intensity ratings for all tested odors.

The role of the amygdala in the perception of positive emotions: an "intensity detector".

The specific role of the amygdala remains controversial even though the development of functional imaging techniques has established its implication in the emotional process. The aim of this study was to highlight the sensitivity of the amygdala to emotional intensity (arousal). We conducted an analysis of the modulation of amygdala activation according to variation in emotional intensity via an fMRI event-related protocol. Monitoring of electrodermal activity, a marker of psychophysiological emotional perception and a reflection of the activation of the autonomic nervous system, was carried out concurrently. Eighteen subjects (10 men; aged from 22 to 29 years) looked at emotionally positive photographs. We demonstrated that the left and right amygdalae were sensitive to changes in emotional intensity, activating more in response to stimuli with higher intensity. Furthermore, electrodermal responses were more frequent for the most intense stimuli, demonstrating the concomitant activation of the autonomic nervous system. These results highlight the sensitivity of the amygdala to the intensity of positively valenced visual stimuli, and in conjunction with results in the literature on negative emotions, reinforce the role of the amygdala in the perception of intensity.

Rule-based category use in preschool children.

We report two experiments suggesting that development of rule use in children can be predicted by applying metrics of complexity from studies of rule-based category learning in adults. In Experiment 1, 124 3- to 5-year-olds completed three new rule-use tasks. The tasks featured similar instructions but varied in the complexity of the rule structures that could be abstracted from the instructions. This measure of complexity predicted children's difficulty with the tasks. Children also completed a version of the Advanced Dimensional Change Card Sorting task. Although this task featured quite different instructions from those in our "complex" task, performance on these two tasks was correlated, as predicted by the rule-based category approach. Experiment 2 predicted findings of the relative difficulty of the three new tasks in 36 5-year-olds and also showed that response times varied with rule structure complexity. Together, these findings suggest that children's rule use depends on processes also involved in rule-based category learning. The findings likewise suggest that the development of rule use during childhood is protracted, and the findings bolster claims that some of children's difficulty in rule use stems from limits in their ability to represent complex rule structures.

An fMRI study on the influence of sommeliers' expertise on the integration of flavor.

Flavors guide consumers' choice of foodstuffs, preferring those that they like and meet their needs, and dismissing those for which they have a conditioned aversion. Flavor affects the learning and consumption of foods and drinks; what is already well-known is favored and what is new is apprehended. The flavor of foodstuffs is also crucial in explaining some eating behaviors such as overconsumption. The "blind" taste test of wine is a good model for assessing the ability of people to convert mouth feelings into flavor. To determine the relative importance of memory and sensory capabilities, we present the results of an fMRI neuro-imaging study involving 10 experts and 10 matched control subjects using wine as a stimulus in a blind taste test, focusing primarily on the assessment of flavor integration. The results revealed activations in the brain areas involved in sensory integration, both in experts and control subjects (insula, frontal operculum, orbitofrontal cortex, amygdala). However, experts were mainly characterized by a more immediate and targeted sensory reaction to wine stimulation with an economic mechanism reducing effort than control subjects. Wine experts showed brainstem and left-hemispheric activations in the hippocampal and parahippocampal formations and the temporal pole, whereas control subjects showed activations in different associative cortices, predominantly in the right hemisphere. These results also confirm that wine experts work simultaneously on sensory quality assessment and on label recognition of wine.

A modular, computer-controlled system for olfactory stimulation in the MRI environment.

Although the cerebral networks involved in sensory perception are of general interest in neuroscience, registration of the effects of olfactory stimulation, especially in a magnetic resonance imaging (MRI) environment, presents particular problems and constraints. This article presents details of a reliable and portable system for olfactory stimulation that is modular in design and based on microcontroller technology. It has the following characteristics: (1) It is under software control; (2) the presentation of olfactory stimulation can be synchronized with respiration; (3) it can be manually controlled; and (4) it is fully compatible with an MRI environment. The principle underlying this system is to direct an odor to the subject's nostrils by switching airflow to different odor diffusers. The characteristics of this system were established using (1) ultraviolet (UV) spectroscopy, to measure its response time, and (2) gas chromatography, to measure the repeatability of odor presentation in terms of gas concentration. A response time of 200 ± 25 ms was obtained for the system, and the standard deviations of the gas concentration delivered during stimulation ranged from 1.5% to 22%, depending on the odor, the airflow, and the dilution of the odor used. Since it is portable, controlled by software, and reliable, on the basis of the results we obtained, this system will lend itself to a wide range of applications in olfactory neuroscience.

Effects of an ambient odor on brain activations during episodic retrieval of objects.

This study investigated the brain areas involved in episodic memory retrieval of pictures depending on the characteristics of the contextual environment during encoding (i.e. presence or absence of an odor). In the first stage, subjects were presented with a series of 32 pictures. Half of the pictures were presented while the subjects smelled an odor (vanillin). No particular odor was associated with the presentation of the other half of the pictures. Two weeks later, a retrieval task was performed in which the same pictures were presented during an fMRI session but without any odor association involved. The results show that both conditions activate a common episodic memory network including the hippocampal formation. Compared with the "encoding without odor" condition, the "encoding with odor" condition shows greater activations in temporal, parietal and frontal cortices, notably within the area of the orbitofrontal cortex which constitutes a main site of the secondary olfactory cortex. No activated areas were observed in the inverse contrast. These results highlight the complexity of the networks involved in episodic memory according to the context during encoding.

Fear-like behavioral responses in mice in different odorant environments: Trigeminal versus olfactory mediation under low doses.

Odors can have repulsive effects on rodents based on two complementary adaptive behaviors: the avoidance of predator odors (potentially dangerous) and the avoidance of trigeminal stimulants (potentially noxious). The present study aimed to compare the behavioral effects on mice of odors according to their trigeminal properties and ecological significance. We used three different odors: 2,4,5-trimethylthiazoline (TMT: a fox feces odor frequently used to elicit fear-induced behaviors), toluene (a strong stimulant of the trigeminal system) and phenyl ethyl alcohol (PEA: a selective stimulant of the olfactory system). First, we checked preference and avoidance behaviors in mice with and without anosmia towards these odors to ensure their olfactory/trigeminal properties. Secondly, we used a standard test (open-field and elevated plus-maze) to assess the behaviors of mice when exposed to these odors. The results show that the anosmic and control mice both avoided TMT and toluene odors. In the open-field and the elevated plus-maze, mice exhibited "anxious" behaviors when exposed to TMT. Conversely, exposure to PEA induced "anxiolytic" effects confirmed by low blood corticosterone levels resulting from completion of the elevated plus-maze. Compared with TMT exposure, toluene exposure induced moderate "anxious" effects.

Odor perception in alexithymic patients.

Alexithymia is characterized by a marked inability to identify feelings and emotional states and some studies have documented sensorial perception in response to visual or auditory cues in this disease. Although olfaction is well known for its emotional correlates, the perception of olfactory stimulations has not been previously investigated. This study compares with standard psychophysical methods the olfactory sensitivity and the self-ratings of intensity and hedonic valence of a panel of odorants in alexithymic patients, non-alexithymic patients and control subjects. Results show that alexithymics over-evaluate intensity and pleasantness of odorants compared to non-alexithymics or control subjects. This could be interpreted in the framework of a lack of inhibitory control including this particular sense.

Enhancement of spatial learning by predator odor in mice: involvement of amygdala and hippocampus.

Olfaction has particular links with learning and memory compared with other sensory cues, due to the interrelations between their neural circuitry. The present study deals with the effects of a putative stressor (i.e. a predator odor) on visuo-spatial learning in mice. Firstly, the results show that a predator odor spread during the Morris water maze task led to learning enhancement. In addition, a stereotaxic approach was used to investigate the involvement of the amygdala in this hippocampus-dependent type of learning. Thus, the performance of mice in visuo-spatial learning under predator odor conditions was dramatically reduced by an ibotenate bilateral amygdala lesion. The involvement of the amygdala was confirmed by a reduced expression of c-fos in the CA1 hippocampus of amygdala-lesioned mice at the end of the learning procedure. Mild exposure to a predator odor during hippocampus-dependent learning therefore leads to an enhancement of performance through the co-activation of the amygdala, probably by a stress mediated mechanism.

Patterns of cerebral activation during olfactory and trigeminal stimulations.

It is well known that most odorants stimulate both the olfactory system and the trigeminal system. However, the overlap between the brain processes involved in each of these sensorial perceptions is still poorly documented. This study aims to compare fMRI brain activations while smelling two odorants of a similar perceived intensity and pleasantness: phenyl ethyl alcohol (a pure olfactory stimulus) and iso-amyl-acetate (a bimodal olfactory-trigeminal stimulus) in a homogeneous sample of 15 healthy, right-handed female subjects. The analysis deals with the contrasts of brain activation patterns between these two odorant conditions. The results showed a significant recruitment of the right insular cortex, and bilaterally in the cingulate in response to the trigeminal component. These findings are discussed in relation to the characteristics of these odorants compared with those tested in previous studies.

Effects of anti-depressants on olfactory sensitivity in mice.

RATIONALE AND OBJECTIVES: Some studies have underlined a decrease in olfactory sensitivity in patients suffering from depression. The present study aims to evaluate the effects of current anti-depressant drugs on the olfactory sensitivity in mice. METHODS MICE: (N degrees =22) were tested in a Y-maze with a choice between an odorant (butanol) or distilled water before and during 3 weeks of daily intra-peritoneal injection of either citalopram or clomipramine. Their performance was compared with those of a control group (N degrees =11) injected with a saline solution. RESULTS: The results showed a significant decrease in olfactory sensitivity with both anti-depressants during the three weeks of treatment. CONCLUSION: The antidepressant induced alteration in serotonin and/or noradrenaline transmission in the olfactory bulb may account for the altered olfactory sensitivity observed in this study.

Odor perception in patients with mood disorders.

BACKGROUND: Olfaction has obvious correlates with emotional processes but little is known about the several aspects of olfaction in psychiatric disorders characterized by mood disturbance. This research aims at pointing out the specificities of olfactory perception in patients in order to identify the specific cerebral impairments involved in these disorders. METHODS: Olfactory sensitivity, detection, identification, self-evaluation of intensity and pleasantness have been recorded in a control group of healthy subjects (N = 58) and in three sample populations admitted to a Psychiatry Department: depressive patients (N = 49), anorectic patients (N = 17), and patients suffering from addiction to alcohol or drugs (N = 21). RESULTS: Depressive patients have a poor sensitivity, poor detection abilities but over-evaluate the pleasantness of odors. Anorectic patients have a high sensitivity, over-evaluate the intensities of the odors but under-evaluate their pleasantness. Alcoholic/drug addicted patients showed impairments in identification. LIMITATION: This study does not identify inter-individual differences in olfactory perception. CONCLUSION: The psychiatric diseases, here at hand although every one of them may be characterized by depressive components, show diverging impairments in olfactory perception. When variations in sensitivity are usually attributed to peripheral cues, impairments in emotional and cognitive aspects of olfaction are typically related to specific brain structures and processes which could be particularly involved in these diseases.

Ambient odors influence the amplitude and time course of visual distraction.

Behavioral performance was examined in a task of attentional capture by luminance under conditions of ambient odors (phenyl ethyl alcohol [PEA], olfactory stimulus, and allyl isothiocyanate [AIC], mixed olfactory/trigeminal stimulus). The AIC increased the amplitude and duration of capture, whereas the presence of PEA led capture to disappear. Furthermore, the PEA caused a general slowing in the speed of information processing. The amplitude and time course of capture were correlated to the irritating components of these odorants, whereas a control experiment showed that the general slowing caused by the PEA was correlated to a drop-off of the subjects' arousal level. These results suggest that ambient odors may exert differential influence of visual-attentional processes and that this influence may depend on the odor's properties.

Left:right differences in psychophysical and electrodermal measures of olfactory thresholds and their relation to electrodermal indices of hemispheric asymmetries.

The study of lateralization processes in olfaction in human subjects has given rise to many contradictory findings. Indeed, sensorial cerebral asymmetry in olfaction depends on several factors (nature of task, quality of stimulus, characteristics of subjects, etc.) and could be also related to differences between the nostrils. In this field, few studies have assessed simultaneously the left-right nostril differences and the hemispheric asymmetry. The present work dealt with this question in the same population with the same odorants, procedures, and stimulations. Seven different concentrations of four specific odorants (two pleasant and two unpleasant) were used by single nostril stimulation with 30 dextral subjects (20 women and 10 men). Threshold detection in unilateral stimulation was investigated using electrodermal response to confirm the first psychophysic measure. Moreover, bilateral recordings of electrodermal activity (EDA) with unilateral stimulation were used as a measure of functional hemispheric asymmetry. Analysis showed no differences between the two nostrils for the threshold detection regardless of the method used (psychophysic or EDA response). However, most subjects presented a constant direction of electrodermal asymmetry whichever nostril was stimulated and whichever odorant stimulus used. The constant bilateral differences in EDA recordings are discussed in terms of asymmetrical activation of the hemispheres.