The widely accepted view nowadays is that experiencing odours as rather pleasant or unpleasant is, to a certain degree, shaped on a daily basis through individual experience within one's culture via evaluative conditioning or, rather marginally so, via mere exposure to that certain odour. In other words, humans are not born with any fixed set of olfactory likes or dislikes but rather, they acquire them throughout their lifetime. However, olfactory sensation is not a "pure" percept, as odorant stimuli generally elicit a qualitative percept of an odorant - generated mainly by the olfactory nerve - as well as some degree of chemesthesis - a tactile confound of the odour generated mainly by the trigeminal nerve. The olfactory and trigeminal system exhibit complex interactions at both the peripheral and central level of chemosensory processing, which is also reflected in perceptual characteristics of the final percept, including perceived pleasantness (hedonics). If the olfactory contribution alone does not easily predict neonatal odour hedonics, due to newborns' limited previous exposure to chemosensory inputs, one may hypothesize that together with the strength of the trigeminal contribution they may form a significant factor affecting neonatal appetitive/aversive responses to odours. In the present...

The present study aimed to investigate intranasal trigeminal sensitivity in a large sample of patients with anosmia due to different etiologies. We investigated the trigeminal detection threshold for formic acid in healthy controls (n = 96) and patients with anosmia due to head trauma (n = 18) or sinonasal disease (n = 54). Anosmics exhibited higher thresholds compared with normosmics (p < 0.001). In addition, thresholds were found to be higher in patients with posttraumatic anosmia compared to anosmics with sinonasal disease (p < 0.001). The data indicate that (1) loss of olfactory sensitivity in humans may be associated with a decreased sensitivity towards trigeminal stimuli and (2) alteration of intranasal trigeminal function is stronger in patients with posttraumatic anosmia compared to patients with sinonasal disease. This may have implications for the medicolegal investigation of anosmic patients where trigeminal stimuli are frequently used to assess the patient’s response bias. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The thesis consists of two parts. The first part introduces the topic of human chemical communication and reviews current evidence on individual variation in human body odour and its perception. This part is framed by sexual selection theory. In the first chapter, the concept of the theory of communication is introduced followed by a discussion on the specifics of chemical communication. Next, the formation of individually specific body odour signatures with reference to skin glands, their volatile products and the subsequent metabolization by skin microflora is described. The next chapters are dedicated to selected interindividual body odour cues such as sex and kin recognition, genetic compatibility in genes of Major Histocompatibility Complex, and health and reproductive status in a mate choice context. Furthermore, interactions between perfumes and body odours are discussed. Finally, methods of body odour sampling are introduced and a rationale behind presenting individual samples or body odour blends is discussed. The second part is comprised of six scientific papers, specifically three reviews and three empirical studies. Review papers summarize factors affecting human body odour quality with emphasis on diet and affective states. The first text shows that human body odours contain cues to...

La cécité précoce induit des changements comportementaux souvent accompagnés par des changements fonctionnels et neuroanatomiques au niveau du cerveau. Alors que les modifications dans les modalités tactiles et auditives ont été largement étudiées, les changements touchant l’olfaction et la douleur chez les aveugles sont restés moins explorés. Chez l’humain aveugle précoce, certaines études ont rapporté une amélioration de la fonction olfactive alors que d’autres n’ont pas réussi à démontrer de tels effets. Chez l’humain, des études récentes ont mis en évidence une hypersensibilité à la douleur aiguë chez les aveugles précoces. Cependant, les mécanismes sous-jacents sont restés inconnus. Afin d’étudier les changements olfactifs et nociceptifs induits par la cécité précoce ainsi que la plasticité fonctionnelle et neuroanatomique qui les accompagne, nous avons développé un modèle de souris de cécité précoce appelé ZRDBA. Dans cette souche, en croisant un parent homozygote pour le gène Rax/Rx (gène responsable de l’anophtalmie) avec un parent hétérozygote, dans une même portée la moitié des souris naissent anophtalmes alors que l’autre moitié a une vue normale. Cette souche nous permet d’examiner les modifications comportementales et cérébrales induites par la cécité chez deux groupes de souris ayant la même base génétique. Le premier objectif de cette thèse était d’évaluer les changements comportementaux olfactifs induits par la cécité chez les souris ZRDBA et d’examiner si ces changements sont accompagnés de plasticité anatomique dans les régions cérébrales impliquées dans le traitement olfactif. Trois tests comportementaux ont été menés : le test de recherche de nourriture, le test du seuil olfactif et le test de performance olfactive. Les résultats ont révélé des meilleures performances olfactives chez les aveugles dans le test de recherche de nourriture ainsi que dans le test de performance olfactive, mais pas dans le test du seuil olfactif. Ces résultats indiquent une amélioration de la discrimination et identification des odeurs chez les souris aveugles. La plasticité cérébrale dans les structures olfactives a été examinée par des analyses histologiques et analyses IRM. Les résultats des mesures histologiques ont révélé une augmentation du volume des bulbes olfactifs, premier relais de traitement des informations olfactives, chez les souris aveugles. Les analyses IRM ont révélé une augmentation du volume dans les couches granulaires et glomérulaires des bulbes olfactifs ainsi que dans d’autres régions impliquées dans ii le traitement olfactif, notamment, le cortex orbitofrontal et le cortex piriforme. Ces résultats suggèrent que l’amélioration de la fonction olfactive chez les souris aveugles peut être expliquée par la plasticité anatomique mise en évidence dans les structures olfactives. Le deuxiéme objectif de cette thèse était d’évaluer la sensibilité à la douleur chez les souris aveugles ZRDBA. Quatre tests nociceptifs ont été réalisés : le test de formaline (sensibilité chimique), le test de Von Frey (sensibilité mécanique), le test d’acétone (sensibilité au froid) et le test de tail-flick dans l’eau (sensibilité au chaud). Les souris aveugles, lorsque comparées à leurs congénères voyantes, ont montré une hypersensibilité à la douleur dans tous les tests. Afin d’examiner les mécanismes sous-jacents de cette hypersensibilité, nous avons investigué par le biais d’analyses immunohistologiques la plasticité fonctionnelle et anatomique dans l’amygdale, structure clé pour la modulation et traitement de la douleur. Les résultats ont montré une augmentation de l’activité c-fos induite par l’injection de la formaline dans le noyau central de l’amygdale et dans toute l’amygdale chez les souris aveugles. Les analyses histologiques ont également montré une augmentation du volume de l’amygdale chez les souris aveugles. Ces résultats suggèrent la contribution de l’amygdale dans l’hypersensibilité à la douleur mise en évidence chez les souris aveugles. Finalement, dans la troisième partie de cette thèse, nous avons voulu investiguer l’impact de la cécité sur la plasticité dans l’ensemble du cerveau à l’aide d’analyses IRM et d’analyses histologiques. Les résultats de cette étude ont révélé une atrophie de la plupart des structures visuelles, notamment, le corps géniculé latéral, le cortex visuel primaire, le cortex visuel secondaire ainsi que les collicules supérieurs. En outre, les analyses histologiques ont révélé une atrophie de la couche IV dans le cortex visuel primaire et dans le cortex visuel secondaire ainsi qu’une atrophie des couches visuelles superficielles des collicules supérieurs chez les souris aveugles expliquant la réduction du volume observée dans ces régions. Dans les autres structures non visuelles, les analyses ont révélé une augmentation du volume dans l’amygdale, impliquée dans la douleur ainsi que dans plusieurs régions olfactives comme les bulbes olfactifs, le cortex piriforme et le cortex orbitofronal chez les souris aveugles. Ces résultats permettent de faire le parallèle avec les études réalisées chez l’humain et ouvrent la porte pour plus d’investigations des mécanismes sous-jacents de la plasticité cérébrale observée chez les aveugles. / Early blindness induces behavioral changes often accompanied by functional and neuroanatomical changes in the brain. While changes in tactile and hearing modalities have been largely investigated, changes in olfaction and pain in the blind remained less explored. While some studies reported an improvement in olfactory function in early blind humans, others failed to demonstrate such effects. In addition, recent studies evidenced hypersensitivity to acute pain in early blind humans. However, the underlying mechanisms remained unknown. In order to study changes induced by early blindness in olfactory function and as well as the underlying functional and neuroanatomical plasticity, we developed a mouse model of early blindness called ZRDBA. In the unique ZRDBA strain, half of the mice homozygous for the Rax / Rx gene (gene responsible for anophthalmia) are born anophthalmic while the other half heterozygous are born sighted. This ZRDBA mice allow investigation of the behavioral and cerebral changes impacts of early blindness without worrying about strain differences. The first aim of this thesis was to assess olfactory changes induced by blindness in ZRDBA mice and examine whether these changes are accompanied by anatomical plasticity in brain regions involved in olfactory processing. Three behavioral tests were conducted: the buried food test, the odor detection threshold test (sensitivity measure) and the olfactory performance test (three-odor discrimination measure). The results revealed better olfactory performance of blind mice the buried food test as well as in the olfactory performance test but not in the olfactory threshold test. These results indicate an improvement in olfactory discrimination and identification in blind mice. Brain plasticity in olfactory structures was examined by histological and MRI analyses. The results of the histological measurements revealed a larger volume of the olfactory bulbs, the first site for processing olfactory information, in blind mice. MRI analysis revealed a larger volume in the granular and glomerular layers of the olfactory bulbs as well as in other regions involved in olfactory processing, namely, the orbitofrontal cortex and the piriform cortex. These results suggest that plasticity in the olfactory structures may explain the improved olfactory function in blind mice. The second aim of this thesis was to assess pain sensitivity in the blind ZRDBA mice. Four nociceptive tests were carried out: the formalin test (chemical sensitivity), the Von Frey iv test (mechanical sensitivity), the acetone test (cold sensitivity) and the water tail-flick test (hot pain sensitivity). Blind mice showed hypersensitivity to pain in all tests. In order to examine the underlying mechanisms of this pain hypersensitivity, we investigated the functional and anatomical plasticity in the amygdala, a key structure for the modulation and treatment of pain using immunohistological analyses. The results revealed an increase of c-Fos activity induced by the injection of formalin in the central nucleus of the amygdala as well as the whole amygdaloid complex in blind mice. Histological measurement also revealed a larger volume of the amygdala in blind mice. These results suggest the contribution of the amygdala in pain hypersensitivity evidenced in blind mice. Finally, in the third part of this thesis, we wanted to investigate the impact of blindness on anatomical plasticity in the whole brain using MRI and histological analyses. The results of this study revealed atrophy of most of the visual structures, in particular, the lateral geniculate nucleus, the primary visual cortex, the secondary visual cortex as well as the superior colliculi. Moreover, histological analyses revealed an atrophy of layer IV of the primary visual cortex and the secondary visual cortex as well as atrophy of the superficial visual layers of the superior colliculus in blind mice explaining the volumetric reduction observed in these regions. In the non-visual structures, analyses revealed a larger volume in the amygdala, as well as in several olfactory structures such as the olfactory bulbs, the piriform cortex and the orbitofronal cortex in blind mice. These results clarify the impact of early blindness on brain plasticity and opens the door for further investigation of its underlying mechanisms.

Emotion, as well as cognition, are often understood as a manifestation of brain activity. However, bodily processes are also involved in mental functioning, referring to the concept of embodiment. Embodied emotion, traditionally, implies that experiencing an emotion involves perceptual, somato-visceral, and motor aspects. Within the frame of the Research Training Group “Situated Cognition”, we here extend the concept of embodiment by considering the role of hormones in the processing of emotional content. Importantly, hormones allow a bidirectional body-to-brain and brain-to-body coupling. The endocrine system, e.g., steroid sex hormones, produced in the gonads, send feedback to the brain by binding at their receptors. These receptors are relatively abundant in the brain regions associated with emotional processing, memory, and executive functions (i.e., amygdala, hippocampus, and prefrontal cortex). Moreover, peripheral hormone secretion is modulated via actions from the central nervous system. We intended to characterize the role of sex hormones, and partly also of stress hormones, on different components of emotion as a hormonal embodiment of emotion. Thus, we examined emotional processing in different sex hormone-status groups. To account for different levels of sex hormones, we used a quasi-experimental approach by comparing women in different cycle phases, women using hormonal oral contraceptives (Study 1), and additionally men (in Study 2). The female menstrual cycle is characterized by fluctuating sex hormone levels. On the peripheral gonadal level, these are 17β-estradiol and progesterone. These hormones are low at the beginning of the cycle (early follicular phase). Estradiol rises towards the middle of the cycle (mid-cycle) and stays moderately high until the next cycle. Progesterone levels are high after mid-cycle in the luteal phase until the end of the cycle. Hormonal contraceptives suppress the endogenous production of estradiol and progesterone, keeping the hormone levels low during the whole cycle. Estradiol and progesterone are also present in males, however, at low levels with no sign of cyclical fluctuations. In Study 1, we examined three independent groups of women in the mid-cycle (n = 24), in the luteal phase (n = 24), and women using hormonal oral contraceptives (n = 24). We assessed different measures of emotional processing, i. e. emotional memory, cognitive and affective empathy-related measures (emotion recognition and ratings for feeling with a protagonist´s emotion, respectively), as well as mimic and skin-conductance responses to affective stimuli. Additionally, we addressed interactions of experimental stress (cold pressor test vs. control) with sex hormones in emotional memory. Our data demonstrated the role of hormones in empathy-related measures and skin-conductance responses depending on the stimulus characteristics (valence, the gender of the protagonist). Emotional memory was not affected by hormone status, stressor or salivary hormone levels. In the cognitive empathy-related measure, women in the luteal phase, as well as oral contraceptive users, identified emotions depicted by female protagonists more accurately than those by male protagonists. On the other hand, estradiol correlated positively with recognition of emotions depicted by males in the total sample. In the affective empathy-related measure, oral contraceptive users rated negative emotions higher than the positive ones. Finally, in the luteal phase skin-conductance responses to negative stimuli were heightened, also supported by a positive correlation with the salivary progesterone levels. The mimic responses remained unaffected. None of the remaining associations with the salivary hormone levels were significant. These results indicate that sex hormones modulated emotional processing by interacting with the stimulus features, as evident in the negativity bias under oral contraceptive use and in the luteal phase in the affective empathy-related measure and sympathetic autonomous reactivity, respectively. However, emotional memory and mimic activity to affective stimuli were not affected. In Study 2, we extended the initial scope to examine the role of sex hormones and olfaction in empathy-related measures. Reports of female advantage in empathy-related measures suggest a role for sex hormones, although data are inconsistent. Studies also report similar sex differences in human olfactory perception. In rodents, olfaction is involved in detecting and integrating socially-relevant information and is modulated by the brain-actions of estrogens. Based on this background, we hypothesized that olfaction may untangle the mixed evidence regarding the relationship between sex hormones and empathy-related measures (cognitive, affective). Thus, we measured odor discrimination ability, empathy-related measures, and facial mimic activity (also associated with affective empathy-related measures) in free-cycling women in high sex-hormone phases (n = 20), oral contraceptive users (n = 19), and men (n = 21). Free-cycling women outperformed only men in the recognition of emotions depicted from the eye region. Oral contraceptive users showed higher scores in the affective empathy-related measure towards negative emotions. Free-cycling women exhibited the strongest facial mimicry (viewing female, but not male protagonists), positively associated with progesterone. Finally, the groups differed in odor discrimination, with free-cycling women outperforming men. However, odor discrimination ability and empathy-related performance were not correlated. Our results support the role of sex hormones in odor perception and empathy-related measures, to a certain extent. However, no common underlying mechanism was found. Finally, we conducted a systematic review (Study 3) aiming to elucidate factors contributing to the inconsistent results concerning the role of sex hormones in the two most addressed areas of emotional processing, emotion recognition (empathy-related measure) and emotional memory. Thereby, we extended previous reviews that address single areas of emotion processing. Moreover, we systematically addressed the role of situational features (mainly emotion-type and/or stimulus valence). All studies included healthy women of reproductive age either in stages of their natural menstrual cycle or using oral contraceptives, and measured or at least estimated levels of ovarian sex hormones. We document the methodological diversity in the field, presumably contributing to the heterogeneity of results. We recognized the need for studies explicitly contrasting the early follicular, mid-cycle, and mid-luteal phases, as well as OC-intake and using standardized tasks. Research would take advantage of using within-subject design more frequently and account for the recognition of complex emotions. In sum, our data suggest that sex hormones differentially modulate the cognitive and affective empathy-related performance and skin-conductance responses by interacting with situational variables, such as the emotional valence of the stimuli and the gender of the protagonist. Women in the luteal phase and under oral contraceptive use demonstrated better recognition of emotions depicted by female protagonists. By contrast, estradiol levels positively correlated with the recognition of emotions depicted by male protagonists. Sex-hormone status main effects only manifested in the emotion recognition advantage of free-cycling women over men (Reading the Mind in The Eyes Test; Study 2). In both studies, affective empathy ratings towards negative emotions were higher in the oral contraceptive users. Moreover, although mimic activity was not associated with sex hormones, skin-conductance responses to negative stimuli were heightened in the luteal phase. On the other hand, the performance in empathy-related measures in different hormone-status groups was not related to odor discrimination ability. Additionally, the inconsistencies of the sex hormone and emotion research could be the result of variations of designs and tasks used across studies from a similar field. This is also indicated in our findings from the empathy-related measures differing in tasks and hormone-status groups in two studies. Finally, our findings provide evidence that emotional processes under sex-hormone modulation are situated, i.e., subject to the influence of the stimulus valence. Furthermore, they are embodied via coupling between the endocrine system and the brain as evident in hormone status and valence interactions in empathy-related measures and sympathetic reactivity.

Objective: Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are of high importance in otorhinolaryngology. Some of their symptoms are related to changes in the nasal trigeminal sensitivity. The aim of this study was to compare nasal trigeminal sensitivity in patients with AR, CRSwNP, and healthy controls (HC). - Methods: A total of 75 individuals participated (age 19–78 years; 34 AR, 10 CRSwNP and 31 HC). Olfactory function was determined using the extended Sniffin’ Sticks test battery. Trigeminal sensitivity was assessed with CO₂ detection thresholds.Trigeminal negative mucosal potentials (NMP) and EEG-derived event-related potentials (ERP) were recorded in response to selective olfactory (phenylethyl alcohol) and trigeminal (CO₂) stimuli using high-precision air-dilution olfactometry. - Results: In comparison to HC, AR patients had lower CO₂ thresholds, also reflected in shorter peak latencies in NMP and trigeminal ERP measurements. CRSwNP patients had a decreased sensitivity for trigeminal stimuli, also reflected in prolonged trigeminal ERP latencies, and reduced olfactory function compared to HC. - Conclusion: AR patients seemed to be more sensitive to trigeminal stimuli than CRSwNP patients. Importantly, the differences could be shown on psychophysical and electrophysiological levels. The changes in trigeminal sensitivity appear to be present already at the level of the respiratory epithelium. The differences between the two groups may depend on the specific inflammatory changes accompanying each disorder, the degree of inflammatory activity, or duration of the inflammatory disorder. However, because the sample sizes are relatively small, these results need to be confirmed in the future studies with larger groups.

Cognitive impairment, “Chemofog”, has been well established as a negative outcome of otherwise successful medical radiation treatments. Mitigation of this negative feature would dramatically increase quality of life for those recovering from cancer treatment. There is currently no known intervention to protect or restore cognitive function of patients undergoing radiation treatments. Development of a multiple ingredient dietary supplement (MDS) is meant to offer a non-invasive therapy to help mitigate risk and decrease damage to individuals. The MDS was originally designed to off-set 5 key mechanisms associated with aging including oxidative damage, inflammation, impaired glucose metabolism, mitochondrial dysfunction and membrane deterioration. Radiation damage shares many of the same deficiencies that develop with age and supplementation with MDS would impact many of the same pathways. Changes in cytokine profile (inflammation markers), and biomarkers of behavioural functions, sensory functions, and oxidative damage provide preliminary evidence of MDS impacts. / Thesis / Bachelor of Science (BSc) / Cognitive impairment, “Chemofog”, has been well established as a negative outcome of otherwise successful medical radiation treatments. Mitigation of this negative feature would dramatically increase quality of life for those recovering from cancer treatment. There is currently no known intervention to protect or restore cognitive function of patients undergoing radiation treatments. Development of a multiple ingredient dietary supplement (MDS) is meant to offer a non-invasive therapy to help mitigate risk and decrease damage to individuals. The MDS was originally designed to off-set 5 key mechanisms associated with aging including oxidative damage, inflammation, impaired glucose metabolism, mitochondrial dysfunction and membrane deterioration. Radiation damage shares many of the same deficiencies that develop with age and supplementation with MDS would impact many of the same pathways.

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Chemosensation is achieved through the binding of chemical signals to chemoreceptor proteins embedded in the membranes of sensory neurons. The molecular identity of these receptors, as well as the downstream processing of chemosensory signals, has been well studied in arthropods and vertebrates. However, very little is known about molluscan chemosensation. The identity of chemoreceptor proteins in the nudibranch mollusc Berghia stephanieae are unknown. Data from other protostome and molluscan studies suggest Berghia may use ionotropic receptors for some forms of chemoreception. This study used a bioinformatics approach to identify potential chemosensory ionotropic receptors in the transcriptome of Berghia. A hidden Markov model program was used to generate molecular profiles of previously identified chemosensory receptors in other animals. A Berghia transcriptome was then searched for likely homologous sequences. Candidate sequences were investigated using protein prediction tools and molecular phylogenies. Fourteen ionotropic glutamate receptors (likely synaptic) and five divergent ionotropic receptors were identified. One of these divergent ionotropic receptor sequences, IR-D, may encode a chemosensory receptor and was therefore selected to determine its cellular expression in sensory and brain tissue using in situ hybridization chain reaction. Expression was seen in the rhinophores and oral tentacles of Berghia, as well as in the rhinophore ganglion, cerebral-pleural ganglion, and pedal ganglion. Similar expression patterns were obtained with tissue-specific transcriptomic data. This was the first study to investigate IR-D as a potential chemosensory receptor in molluscs, and thus has helped identify a new family of possible ionotropic chemoreceptor proteins in molluscs. These results have laid the groundwork for continued investigation of Berghia’s chemosensory system.