Olfactory dysfunction, affecting 75-90 % of Parkinson's disease (PD) patients, holds significant predictive value for PD development. Advanced imaging techniques, such as diffusion MRI (dMRI) and functional MRI (fMRI), offer insights into structural and functional changes within olfactory pathways. This review summarizes a decade of research on MRI-based connectivity of the olfactory system in PD, focusing on structural and functional alterations in olfactory brain areas and their links to early olfactory processing changes. Fifteen dMRI and eighteen fMRI studies met inclusion criteria and were carefully reviewed. Among the studies investigating diffusion metrics, the most consistent finding was the reduction of fractional anisotropy in the olfactory tract and anterior olfactory structures, though evidence correlating this result to olfactory dysfunction is limited and contrasting. dMRI support the hypothesis that olfactory function may be correlated to structural alterations at the network-level. In contrast, fMRI studies found more consistent evidence of dysconnectivity in both primary and secondary olfactory areas as directly correlated to olfactory processing and dysfunction. Results suggest a potential dissociation between structural alterations in olfactory brain regions and early functional impairment in olfactory processing, likely related to different patient subtypes. Heterogeneity in clinical and technical factors may limit the generalizability of the results, leaving room for further investigations. By providing a comprehensive perspective on the use of dMRI and fMRI to explore the olfactory connectome in PD, our review might facilitate future research towards earlier diagnosis and more targeted therapeutic and neurorehabilitation strategies.

As people commonly observe dog behaviors like the sudden bursts of physical movement colloquially known as "zoomies," and the canine penchant for sticking their nose out of car windows and for sniffing intently in dog parks, it is not surprising that people generally believe dogs learn and communicate by smell. While people generally discount their own olfactory sensitivity and the importance of smell overall, humans also learn and communicate by smell, in some cases even better than dogs. In this article, we discuss why this information exchange matters for learning and memory and why virtual meetings don't pass the sniff test.

Although chemical signaling is an essential mode of communication in most vertebrates, it has long been viewed as having negligible effects in humans. However, a growing body of evidence shows that the sense of smell affects human behavior in social contexts ranging from affiliation and parenting to disease avoidance and social threat. This article aims to (a) introduce research on human chemical communication in the historical context of the behavioral sciences; (b) provide a balanced overview of recent advances that describe individual differences in the emission of semiochemicals and the neural mechanisms underpinning their perception, that together demonstrate communicative function; and (c) propose directions for future research toward unraveling the molecular principles involved and understanding the variability in the generation, transmission, and reception of chemical signals in increasingly ecologically valid conditions. Achieving these goals will enable us to address some important societal challenges but are within reach only with the aid of genuinely interdisciplinary approaches.

The human brain is organized as a hierarchical global network. Functional connectivity research reveals that sensory cortices are connected to corresponding association cortices via a series of intermediate nodes linked by synchronous neural activity. These sensory pathways and relay stations converge onto central cortical hubs such as the default-mode network (DMN). The DMN regions are believed to be critical for representing concepts and, hence, language acquisition and use. Although prior research has established that major senses are placed at a similar distance from the DMN-five to six connective steps-it is still unknown how the olfactory system functionally connects to the large-scale cortical hubs of the human brain. In this study, we investigated the connective distance from olfactory seed areas to the DMN. The connective distance involves a series of three to four intermediate steps. Furthermore, we parcellated the olfactory cortical subregions and found evidence of two distinct olfactory pathways. One emerges from the anterior olfactory nucleus and olfactory tubercle; it involves early access to the orbitofrontal cortex, known for processing reward and multisensory signals. The other emerges from the frontal and temporal regions of the piriform cortex, involving the anterior insula, intermediate frontal sulcus, and parietal operculum. The results were confirmed in a replication cohort. Our results provide evidence that olfaction has unique early access to the central cortical networks via dual pathways.

Olfactory sensitivity to odorant molecules is a complex biological function influenced by both endogenous factors, such as genetic background and physiological state, and exogenous factors, such as environmental conditions. In animals, this vital ability is mediated by olfactory sensory neurons (OSNs), which are distributed across several specialized olfactory subsystems depending on the species. Using the phosphorylation of the ribosomal protein S6 (rpS6) in OSNs following sensory stimulation, we developed an ex vivo assay allowing the simultaneous conditioning and odorant stimulation of different mouse olfactory subsystems, including the main olfactory epithelium, the vomeronasal organ, and the Grueneberg ganglion. This approach enabled us to observe odorant-induced neuronal activity within the different olfactory subsystems and to demonstrate the impact of environmental conditioning, such as temperature variations, on olfactory sensitivity, specifically in the Grueneberg ganglion. We further applied our rpS6-based assay to the human olfactory system and demonstrated its feasibility. Our findings show that analyzing rpS6 signal intensity is a robust and highly reproducible indicator of neuronal activity across various olfactory systems, while avoiding stress and some experimental limitations associated with in vivo exposure. The potential extension of this assay to other conditioning paradigms and olfactory systems, as well as its application to other animal species, including human olfactory diagnostics, is also discussed.

There is a view that the perception of thirst and actual body fluid balance may affect cognitive and exercise performance. The evolutionary evidence suggests that our survival was dependent on our ability to sweat profusely when hunting during the heat of the day (persistence hunting), so if water deficits were not tolerated, consequently the thirst mechanism would limit our persistence hunting capability. This also means that hunting and searching for water was undertaken with some extent of water deficit, and in turn suggests that performance; physical and cognitive, was conducted with a degree of dehydration. Given the current views on the maintenance of body water for performance, there is a need to evaluate the evidence relating to tolerance limits for water deficits with respect to both physical and cognitive performance. This review considers the thirst mechanism and the conditions and selective pressures under which this might have evolved. Consideration will be given to how the thirst mechanism influences our physical and cognitive performance. The review suggests that Homo developed appropriate tolerances for water deficits and thirst perception, with a safety margin that prevented detrimental declines in physical and cognitive performance to the point of inhibiting corrective action. This would have offered a selective advantage, enabling the search for water and functioning adequately during periods of water scarcity.

This perspective considers the novel concept of olfactory neurofeedback (O-NFB) within the framework of brain-computer interfaces (BCIs), where olfactory stimuli are integrated in various BCI control loops. In particular, electroencephalography (EEG)-based O-NFB systems are capable of incorporating different components of complex olfactory processing - from simple discrimination tasks to using olfactory stimuli for rehabilitation of neurological disorders. In our own work, EEG theta and alpha rhythms were probed as control variables for O-NFB. Additionaly, we developed an olfactory-based instructed-delay task. We suggest that the unique functions of olfaction offer numerous medical and consumer applications where O-NFB is combined with sensory inputs of other modalities within a BCI framework to engage brain plasticity. We discuss the ways O-NFB could be implemented, including the integration of different types of olfactory displays in the experiment set-up and EEG features to be utilized. We emphasize the importance of synchronizing O-NFB with respiratory rhythms, which are known to influence EEG patterns and cognitive processing. Overall, we expect that O-NFB systems will contribute to both practical applications in the clinical world and the basic neuroscience of olfaction.

Olfaction may play a restricted role in human behavior, yet paradoxically, its absence in anosmia is associated with diverse deleterious outcomes, culminating in reduced life expectancy. The mammalian nose serves two purposes: olfaction and breathing. Because respiratory patterns are impacted by odors, we hypothesized that nasal respiratory airflow may be altered in anosmia. We apply a wearable device that precisely logs nasal airflow for 24-hour-long sessions in participants with isolated congenital anosmia and controls. We observe significantly altered patterns of respiratory nasal airflow in anosmia in wake and in sleep. These differences allow classification of anosmia at 83% accuracy using the respiratory trace alone. Patterns of respiratory airflow have pronounced impact on health, emotion and cognition. We therefore suggest that a portion of the deleterious outcomes associated with anosmia may be attributed to altered patterns of respiratory nasal airflow rather than a direct result of lost odor perception per se.

Olfaction is a fundamental sensory modality that guides animal and human behaviour1,2. However, the underlying neural processes of human olfaction are still poorly understood at the fundamental-that is, the single-neuron-level. Here we report recordings of single-neuron activity in the piriform cortex and medial temporal lobe in awake humans performing an odour rating and identification task. We identified odour-modulated neurons within the piriform cortex, amygdala, entorhinal cortex and hippocampus. In each of these regions, neuronal firing accurately encodes odour identity. Notably, repeated odour presentations reduce response firing rates, demonstrating central repetition suppression and habituation. Different medial temporal lobe regions have distinct roles in odour processing, with amygdala neurons encoding subjective odour valence, and hippocampal neurons predicting behavioural odour identification performance. Whereas piriform neurons preferably encode chemical odour identity, hippocampal activity reflects subjective odour perception. Critically, we identify that piriform cortex neurons reliably encode odour-related images, supporting a multimodal role of the human piriform cortex. We also observe marked cross-modal coding of both odours and images, especially in the amygdala and piriform cortex. Moreover, we identify neurons that respond to semantically coherent odour and image information, demonstrating conceptual coding schemes in olfaction. Our results bridge the long-standing gap between animal models and non-invasive human studies and advance our understanding of odour processing in the human brain by identifying neuronal odour-coding principles, regional functional differences and cross-modal integration.

As information acquisition terminals for artificial olfaction, chemiresistive gas sensors are often troubled by their cross-sensitivity, and reducing their cross-response to ambient gases has always been a difficult and important point in the gas sensing area. Pattern recognition based on sensor array is the most conspicuous way to overcome the cross-sensitivity of gas sensors. It is crucial to choose an appropriate pattern recognition method for enhancing data analysis, reducing errors and improving system reliability, obtaining better classification or gas concentration prediction results. In this review, we analyze the sensing mechanism of cross-sensitivity for chemiresistive gas sensors. We further examine the types, working principles, characteristics, and applicable gas detection range of pattern recognition algorithms utilized in gas-sensing arrays. Additionally, we report, summarize, and evaluate the outstanding and novel advancements in pattern recognition methods for gas identification. At the same time, this work showcases the recent advancements in utilizing these methods for gas identification, particularly within three crucial domains: ensuring food safety, monitoring the environment, and aiding in medical diagnosis. In conclusion, this study anticipates future research prospects by considering the existing landscape and challenges. It is hoped that this work will make a positive contribution towards mitigating cross-sensitivity in gas-sensitive devices and offer valuable insights for algorithm selection in gas recognition applications.

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.

This study evaluates the performance advancement of electronic noses, on-chip engineered multisensor systems, exploiting a combinatorial approach. We analyze a spectrum of metal oxide semiconductor materials produced by individual methods of liquid-phase synthesis and a combination of chemical deposition and sol-gel methods with hydrothermal treatment. These methods are demonstrated to enable obtaining a fairly wide range of nanomaterials that differ significantly in chemical composition, crystal structure, and morphological features. While synthesis routes foster diversity in material properties, microplotter printing ensures targeted precision in making on-chip arrays for evaluation of a combinatorial selectivity concept in the task of organic vapor, like alcohol homologs, acetone, and benzene, classification. The synthesized nanomaterials demonstrate a high chemiresistive response, with a limit of detection beyond ppm level. A specific combination of materials is demonstrated to be relevant when the number of sensors is low; however, such importance diminishes with an increase in the number of sensors. We show that on-chip material combinations could favor selectivity to a specific analyte, disregarding the others. Hence, modern synthesis methods and printing protocols supported by combinatorial analysis might pave the way for fabricating on-chip orthogonal multisensor systems.

The sense of smell is an important mediator of health and sociality at all stages of life, yet it has received limited attention in our lineage. Olfaction starts in utero and participates in the establishment of social bonds in children, and of romantic and sexual relationships after puberty. Smell further plays a key role in food assessment and danger avoidance; in modern societies, it also guides our consumer behavior. Sensory abilities typically decrease with age and can be impacted by diseases, with repercussions on health and well-being. Here, we critically review our current understanding of human olfactory communication to refute outdated notions that our sense of smell is of low importance. We provide a summary of the biology of olfaction, give a prospective overview of the importance of the sense of smell throughout the life course, and conclude with an outline of the limitations and future directions in this field.

The dietary choices a mother makes during pregnancy offer her developing fetus its earliest exposure to the family's culinary preferences. This comprehensive literature review synthesizes five decades of research, which has provided valuable insights into fetal flavor learning. Converging evidence across various species supports the functionality of fetal chemoreceptive systems by the end of gestation, enabling the detection of an extensive array of chemosensory cues derived from the maternal diet and transmitted to the amniotic fluid. The fetus effectively encodes these flavors, resulting in their enhanced acceptance after birth. While existing studies predominantly concentrate on fetal learning about odor volatiles, limited evidence suggests a capacity for learning about gustatory (i.e., taste) properties. Examining whether these prenatal odor, taste, and flavor experiences translate into enduring shifts in dietary behaviors beyond weaning remains a crucial avenue for further investigation.

Cartilaginous fishes have large and elaborate olfactory organs, but only a small repertoire of olfactory receptor genes. Here, we quantitatively analyze the olfactory system of 21 species of sharks and rays, assessing many features of the olfactory organ (OOR) (number of primary lamellae, branches of the secondary folds, sensory surface area, and density and number of sensory neurons) and the olfactory bulb (OB) (number of neurons and non-neuronal cells), and estimate the ratio between the number of neurons in the two structures. We show that the number of lamellae in the OOR does not correlate with the sensory surface area, while the complexity of the lamellar shape does. The total number of olfactory receptor neurons ranges from 30.5 million to 4.3 billion and the total number of OB neurons from 1.5 to 90 million. The number of neurons in the olfactory epithelium is 16 to 158 times higher (median ratio is 46) than the number of neurons in the OB. These ratios considerably exceed those reported in mammals. High convergence from receptor neurons to neurons processing olfactory information, together with the remarkably small olfactory receptor repertoire, strongly suggests that the olfactory system of sharks and rays is well adapted to detect a limited number of odorants with high sensitivity.

Hormone changes across women's menstrual cycles may lead to changes in their perceptions of chemical signals and their hormonal responses to these cues. The aim of the present study was to determine the role of menstrual cycle phase in the response to extracts of male axillary secretions (EMAS) in women. We tested healthy reproductive age and premenopausal women (n = 29). An EMAS/control solution was applied once every two hours during either the follicular or luteal phase, at which point saliva samples for luteinizing hormone (LH) and cortisol monitoring were collected. LH and cortisol concentrations were analyzed using the enzyme immunoassay (EIA) technique. Positive and Negative Affect Schedule (PANAS) and Visual Analogue Scales (VAS) scores were used to assess the participants' moods. For the first time, we showed that EMAS may produce opposite effects on LH secretion depending on the menstrual cycle phase of the recipient. We observed a significant increase in the number of LH peaks (p = 0.0447) and their amplitudes (p = 0.0469) when EMAS was applied during the follicular phase, while the same application in the luteal phase lowered the amplitudes of LH peaks (p = 0.0382). For the first time, we showed that EMAS application increased salivary cortisol levels in reproductive age women relative to premenopausal women (p = 0.0032). PANAS scores revealed changes in positive and negative affect after EMAS application. Our data indicate the significance of the menstrual cycle phase for EMAS' effects on LH secretion and mood, but not on cortisol secretion in women.

Humans naturally integrate signals from the olfactory and intranasal trigeminal systems. A tight interplay has been demonstrated between these two systems, and yet the neural circuitry mediating olfactory-trigeminal (OT) integration remains poorly understood. Using functional magnetic resonance imaging (fMRI), combined with psychophysics, this study investigated the neural mechanisms underlying OT integration. Fifteen participants with normal olfactory function performed a localization task with air-puff stimuli, phenylethyl alcohol (PEA; rose odor), or a combination thereof while being scanned. The ability to localize PEA to either nostril was at chance. Yet, its presence significantly improved the localization accuracy of weak, but not strong, air-puffs, when both stimuli were delivered concurrently to the same nostril, but not when different nostrils received the two stimuli. This enhancement in localization accuracy, exemplifying the principles of spatial coincidence and inverse effectiveness in multisensory integration, was associated with multisensory integrative activity in the primary olfactory (POC), orbitofrontal (OFC), superior temporal (STC), inferior parietal (IPC) and cingulate cortices, and in the cerebellum. Multisensory enhancement in most of these regions correlated with behavioral multisensory enhancement, as did increases in connectivity between some of these regions. We interpret these findings as indicating that the POC is part of a distributed brain network mediating integration between the olfactory and trigeminal systems. PRACTITIONER POINTS: Psychophysical and neuroimaging study of olfactory-trigeminal (OT) integration. Behavior, cortical activity, and network connectivity show OT integration. OT integration obeys principles of inverse effectiveness and spatial coincidence. Behavioral and neural measures of OT integration are correlated.

The world is undergoing massive atmospheric and ecological change, driving unprecedented challenges to human well-being. Olfaction is a key sensory system through which these impacts occur. The sense of smell influences quality of and satisfaction with life, emotion, emotion regulation, cognitive function, social interactions, dietary choices, stress, and depressive symptoms. Exposures via the olfactory pathway can also lead to (anti-)inflammatory outcomes. Increased understanding is needed regarding the ways in which odorants generated by nature (i.e., natural olfactory environments) affect human well-being. With perspectives from a range of health, social, and natural sciences, we provide an overview of this unique sensory system, four consensus statements regarding olfaction and the environment, and a conceptual framework that integrates the olfactory pathway into an understanding of the effects of natural environments on human well-being. We then discuss how this framework can contribute to better accounting of the impacts of policy and land-use decision-making on natural olfactory environments and, in turn, on planetary health.

In navigating the complexities of social life, humans have evolved to interpret invisible odorous chemical cues, with profound behavioural impacts often unbeknown to the conscious mind. The manifestation of this in humans is evident in the scent of androstadienone (androsta-4,16-dien-3-one), an odorous compound which is considered a putative human pheromone. The current study investigated the effect of androstadienone on social distance-dependent prosocial behaviour measured by a social discounting task, in which participants chose between selfish and generous options. Based on our pre-registration, we predicted a sex-specific effect, with males exposed to androstadienone exhibiting increased generosity, while females would choose more selfishly. Employing a double-blind, placebo-controlled, between-subject design, we recruited 170 participants who were randomly assigned to either the androstadienone or control condition. Olfactory stimuli were administered while participants completed the social discounting task. Inconsistent with our hypothesis, inhaling androstadienone did not impact social distance-dependent prosocial behaviour. This finding was supported by multiple estimates of prosociality, including model-free, model-based and maximum likelihood estimation. Further analyses indicated that androstadienone administration did not influence perceived social distance or bias participants towards being generous or selfish. Thus, our empirical findings provide no support for the hypothesis that androstadienone modulates generosity.

Among the numerous long COVID symptoms, olfactory dysfunction persists in ∼10 % of patients suffering from SARS-CoV-2 induced anosmia. Among the few potential therapies, corticoid treatment has been used for its anti-inflammatory effect with mixed success in patients. In this study, we explored its impact using hamster as an animal model. SARS-CoV-2 infected hamsters lose their smell abilities and this loss is correlated with damage of the olfactory epithelium and persistent presence of innate immunity cells. We started a dexamethasone treatment 2 days post infection, when olfaction was already impacted, until 11 days post infection when it started to recover. We observed an improvement of olfactory capacities in the animals treated with corticoid compared to those treated with vehicle. This recovery was not related to differences in the remaining damage to the olfactory epithelium, which was similar in both groups. This improvement was however correlated with a reduced inflammation in the olfactory epithelium with a local increase of the mature olfactory neuron population. Surprisingly, at 11 days post infection, we observed an increased and disorganized presence of immature olfactory neurons, especially in persistent inflammatory zones of the epithelium. This unusual population of immature olfactory neurons coincided with a strong increase of olfactory epithelium proliferation in both groups. Our results indicate that persistent inflammation of the olfactory epithelium following SARS-CoV-2 infection may alter the extent and speed of regeneration of the olfactory neuron population, and that corticoid treatment is effective to limit inflammation and improve olfaction recovery following SARS-CoV-2 infection.

Electronic nose devices stand out as pioneering innovations in contemporary technological research, addressing the arduous challenge of replicating the complex sense of smell found in humans. Currently, sensor instruments find application in a variety of fields, including environmental, (bio)medical, food, pharmaceutical, and materials production. Particularly the latter, has seen a significant increase in the adoption of technological tools to assess food quality, gradually supplanting human panelists and thus reshaping the entire quality control paradigm in the sector. This process is happening even more rapidly in the world of wine, where olfactory sensory analysis has always played a central role in attributing certain qualities to a wine. In this review, conducted using sources such as PubMed, Science Direct, and Web of Science, we examined papers published between January 2015 and January 2024. The aim was to explore prevailing trends in the use of human panels and sensory tools (such as the E-nose) in the wine industry. The focus was on the evaluation of wine quality attributes by paying specific attention to geographical origin, sensory defects, and monitoring of production trends. Analyzed results show that the application of E-nose-type sensors performs satisfactorily in that trajectory. Nevertheless, the integration of this type of analysis with more classical methods, such as the trained sensory panel test and with the application of destructive instrument volatile compound (VOC) detection (e.g., gas chromatography), still seems necessary to better explore and investigate the aromatic characteristics of wines.

Pet food production is a fast-growing industry. While extruded dry pet food is the favored pet food due to its convenience of use, it may have poorer palatability than other pet foods such as wet pet foods. However, palatability plays a pivotal role in meeting nutritional requirements or providing therapeutic benefits in cats and dogs, as it ensures food acceptance. Thus, both academics and manufacturers conduct routine palatability tests to assess acceptance and preference of products among pets, alongside sensory analyses involving human panels. Palatability is greatly influenced by species-specific and environmental factors in cats and dogs. The review will hence present the current knowledge on palatability assessment and animal food perception; it will then aim to explore strategies for effectively managing palatability in dry pet food by examining the impact of key ingredients and process parameters on the finished product's palatability. Moreover, the demands and needs for sustainable and healthier products as well as supply constraints present novel challenges and opportunities for academics and manufacturers.

Domestic dogs (Canis familiaris) have excellent olfactory processing capabilities that are utilized widely in human society e.g., working with customs, police, and army; their scent detection is also used in guarding, hunting, mold-sniffing, searching for missing people or animals, and facilitating the life of the disabled. Sniffing and searching for odors is a natural, species-typical behavior and essential for the dog's welfare. While taking advantage of this canine ability widely, we understand its foundations and implications quite poorly. We can improve animal welfare by better understanding their olfactory world. In this review, we outline the olfactory processing of dogs in the nervous system, summarize the current knowledge of scent detection and differentiation; the effect of odors on the dogs' cognitive and emotional processes and the dog-human bond; and consider the methodological advancements that could be developed further to aid in our understanding of the canine world of odors.

As highly promising devices for odor recognition, current electronic noses are still not comparable to human olfaction due to the significant disparity in the number of gas sensors versus human olfactory receptors. Inspired by the sniffing skills of wine tasters to achieve better odor perception, a multiple overlapping sniffs (MOSS) strategy is proposed in this study. The MOSS strategy involves rapid and continuous inhalation of odorants to stimulate the sensor array to generate feature-rich temporal signals. Computational fluid dynamics simulations are performed to reveal the mechanism of complex dynamic flows affecting transient responses. The proposed strategy shows over 95% accuracy in the recognition experiments of three gaseous alkanes and six liquors. Results demonstrate that the MOSS strategy can accurately and easily recognize odors with a limited sensor number. The proposed strategy has potential applications in various odor recognition scenarios, such as medical diagnosis, food quality assessment, and environmental surveillance.

Historically, the human sense of smell has been regarded as the odd stepchild of the senses, especially compared to the sensory bravado of seeing, touching, and hearing. The idea that the human olfaction has little to contribute to our experience of the world is commonplace, though with the emergence of COVID-19 there has rather been a sea change in this understanding. An ever increasing body of work has convincingly highlighted the keen capabilities of the human nose and the sophistication of the human olfactory system. Here, we provide a concise overview of the neuroscience of human olfaction spanning the last 10-15 years, with focus on the peripheral and central mechanisms that underlie how odor information is processed, packaged, parceled, predicted, and perturbed to serve odor-guided behaviors. We conclude by offering some guideposts for harnessing the next decade of olfactory research in all its shapes and forms.

The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. However, the lateralization of olfactory processes is known to depend on the task and nature of stimuli. It still remains unclear whether olfactory system projections in humans also correspond to functional pathways during olfactory tasks without any trigeminal, perceptual, or cognitive-motor components. Twenty young healthy subjects with a normal sense of smell took part in an olfactory functional magnetic resonance imaging (fMRI) study. We used 2 types of nostril-specific stimulation, passive (no sniffing), and active (with sniffing), with phenyl ethyl alcohol, a pure olfactory stimulant, to investigate fMRI activity patterns in primary and secondary olfactory-related brain structures. Irrespective of the stimulated nostril and the type of stimulation, we detected symmetrical activity in primary and secondary olfactory-related brain structures such as the primary olfactory cortex, entorhinal cortex, and orbitofrontal cortex. In the absence of perceptual or cognitive-motor task demands, the perception of monorhinally presented pure odors is processed bilaterally in the brain.

Despite the predominant focus on visual perception in most studies, the role of humans' sense of smell in navigation has often been neglected. Recent research, however, could show that humans are indeed able to use their sense of smell for orientation, particularly when processed implicitly. In this study, we investigate whether implicit perception of olfactory landmarks enhanced wayfinding performance compared to explicit perception. Fifty-two people completed a wayfinding and a recognition task in a virtual maze at two times of testing 1 month apart. Participants either received olfactory, visual, or both cues at the intersections. Wayfinding performance was better for olfactory landmarks, which were not correctly remembered in the recognition task. In contrast, wayfinding performance was better when visual landmarks were correctly remembered. In the multimodal condition, wayfinding performance was better with landmarks being remembered at t1 and remained the same at t2. Our results suggest distinct implicit processing mechanisms within the olfactory system and therefore hold important implications for the nature of spatial odor processing extending beyond explicit odor localization tasks. The study highlights the importance for future studies to develop and employ further experimental methods that capture implicit processing across all of our senses. This is crucial for a comprehensive understanding of consciousness, as olfaction strongly influences our behavior, but remains largely latent unless deliberately honed through practice.

Olfaction is one of the five basic human senses, and it is known to be one of the most primitive senses. The sense of olfaction may have been critical for human survival in prehistoric society, and although many believe its importance has diminished over time, it continues to have an impact on human interaction, bonding, and propagation of the species. Even if we are unaware of it, the sense of smell greatly affects our lives and is closely related to overall quality of life and health. Nonetheless, olfaction has been neglected from a scientific perspective compared to other senses. However, olfaction has recently received substantial attention since the loss of smell and taste has been noted as a key symptom of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Studies investigating olfaction loss in association with coronavirus disease 2019 (COVID-19) have revealed that olfactory dysfunction can be both conductive and sensorineural, possibly causing structural changes in the brain. Olfactory training is an effective treatment for olfactory dysfunction, suggesting the reorganization of neural associations. A reduced ability to smell may also alert suspicion for neurodegenerative or psychiatric disorders. Here, we summarize the basic knowledge that we, as otorhinolaryngologists, should have about the sense of smell and the peripheral and central olfactory pathways for managing and helping patients with olfactory dysfunction.

This study addresses the paucity of research concerning the subjective experiences of those affected by anosmia. In the study, we interviewed individuals(n = 11) recruited via the charity (Fifth Sense) and used Interpretative Phenomenological Analysis (IPA) to analyse the data. Findings revealed three main themes and seven sub themes. The main themes are Living with Anosmia; Remembrance of things old and new and Resilience. The study reveals the process of becoming aware of being anosmic and the relationships with others in this process including potentially unhelpful minimisations of the impact by professionals. In addition to a sense of isolation and insecurity, living with anosmia for some participants brought with it an identification of being 'anosmic' and feeling part of a community. This was in contrast to a general lack of public knowledge and understanding of anosmia. The findings of the study demonstrated the importance of smell to time, place and relationship and the recalling of smells as bringing a sense of connectivity to loved ones, of times past and also a sense of loss of ability. Participants also described the ways in which they coped and adapted to a life with anosmia and focused on positive aspects of life. These findings provide a rich qualitative account of the experience of anosmia. The findings point towards future research which could inform us about the lives of those who are anosmic and currently unaware and of those recently diagnosed, which will create a richer understanding of the experiences of anosmia.

Humans produce odorous secretions from multiple body sites according to the microbiomic profile of each area and the types of secretory glands present. Because the axilla is an active, odor-producing region that mediates social communication via the sense of smell, this article focuses on the biological mechanisms underlying the creation of axillary odor, as well as the intrinsic and extrinsic factors likely to impact the odor and determine individual differences. The list of intrinsic factors discussed includes sex, age, ethnicity, emotions, and personality, and extrinsic factors include dietary choices, diseases, climate, and hygienic habits. In addition, we also draw attention to gaps in our understanding of each factor, including, for example, topical areas such as the effect of climate on body odor variation. Fundamental challenges and emerging research opportunities are further outlined in the discussion. Finally, we suggest guidelines and best practices based on the factors reviewed herein for preparatory protocols of sweat collection, data analysis, and interpretation.

Anosmia, the loss of the sense of smell, is one of the main neurological manifestations of COVID-19. Although the SARS-CoV-2 virus targets the nasal olfactory epithelium, current evidence suggests that neuronal infection is extremely rare in both the olfactory periphery and the brain, prompting the need for mechanistic models that can explain the widespread anosmia in COVID-19 patients. Starting from work identifying the non-neuronal cell types that are infected by SARS-CoV-2 in the olfactory system, we review the effects of infection of these supportive cells in the olfactory epithelium and in the brain and posit the downstream mechanisms through which sense of smell is impaired in COVID-19 patients. We propose that indirect mechanisms contribute to altered olfactory system function in COVID-19-associated anosmia, as opposed to neuronal infection or neuroinvasion into the brain. Such indirect mechanisms include tissue damage, inflammatory responses through immune cell infiltration or systemic circulation of cytokines, and downregulation of odorant receptor genes in olfactory sensory neurons in response to local and systemic signals. We also highlight key unresolved questions raised by recent findings.

Representational drift is a phenomenon of increasing interest in the cognitive and neural sciences. While investigations are ongoing for other sensory cortices, recent research has demonstrated the pervasiveness in which it occurs in the piriform cortex for olfaction. This gradual weakening and shifting of stimulus-responsive cells has critical implications for sensory stimulus-response models and perceptual decision-making. While representational drift may complicate traditional sensory processing models, it could be seen as an advantage in olfaction, as animals live in environments with constantly changing and unpredictable chemical information. Non-topographical encoding in the olfactory system may aid in contextualizing reactions to promiscuous odor stimuli, facilitating adaptive animal behavior and survival. This article suggests that traditional models of stimulus-(neural) response mapping in olfaction may need to be reevaluated and instead motivates the use of dynamical systems theory as a methodology and conceptual framework.

The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. It is still unclear whether these projections also correspond to functional pathways of odor processing. In an olfactory functional magnetic resonance imaging (fMRI) study of twenty young healthy subjects with a normal sense of smell, we tested whether nostril specific stimulation with phenyl ethyl alcohol (PEA), a pure olfactory stimulant, asymmetrically activates primary or secondary olfactory-related brain structures such as primary olfactory cortex, entorhinal cortex, and orbitofrontal cortex. The results indicated that without a challenging olfactory task, passive (no sniffing) and active (with sniffing) nostril-specific PEA stimulation did not produce asymmetrical fMRI activation in olfactory cortical structures.

Neuronal morphological characterization and behavioral phenotyping in mouse models help dissecting neural mechanisms of brain disorders. Olfactory dysfunctions and other cognitive problems were widely reported in asymptomatic carriers and symptomatic patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This led us to generate the knockout mouse model for Angiotensin Converting Enzyme-2 (ACE2) receptor, one of the molecular factors mediating SARS-CoV-2 entry to the central nervous system, using CRISPR-Cas9 based genome editing tools. ACE2 receptors and Transmembrane Serine Protease-2 (TMPRSS2) are widely expressed in the supporting (sustentacular) cells of human and rodent olfactory epithelium, however, not in the olfactory sensory neurons (OSNs). Hence, acute inflammation induced changes due to viral infection in the olfactory epithelium may explain transient changes in olfactory detectabilities. As ACE2 receptors are expressed in different olfactory centers and higher brain areas, we studied the morphological changes in the olfactory epithelium (OE) and olfactory bulb (OB) of ACE2 KO mice in comparison with wild type animals. Our results showed reduced thickness of OSN layer in the OE, and a decrease in cross-sectional area of glomeruli in the OB. Aberrations in the olfactory circuits were revealed by lowered immunoreactivity toward microtubule associated protein 2 (MAP2) in the glomerular layer of ACE2 KO mice. Further, to understand if these morphological alterations lead to compromised sensory and cognitive abilities, we performed an array of behavioral assays probing their olfactory subsystems' performances. ACE2 KO mice exhibited slower learning of odor discriminations at the threshold levels and novel odor identification impairments. Further, ACE2 KO mice failed to memorize the pheromonal locations while trained on a multimodal task implying the aberrations of neural circuits involved in higher cognitive functions. Our results thus provide the morphological basis for the sensory and cognitive disabilities caused by the deletion of ACE2 receptors and offer a potential experimental approach to study the neural circuit mechanisms of cognitive impairments observed in long COVID.

Human mate value is assessed on numerous variables including, reproductive potential and disease resistance. Many of these variables have been correlated with judgments of physical, vocal, and odor attractiveness. While some researchers posit that attractiveness judgments made across different sensory modalities reflect the same underlying variable(s) (i.e., the information is redundant), others suggest that judgments made in different modalities reflect different variables. Previous studies of human attractiveness indicate that attractiveness judgments of others' faces, bodies, and voices are intercorrelated, which is suggested to support the redundancy hypothesis. Less is known about body odor attractiveness. Only one study has simultaneously investigated the relationships between judgments of body odor, face, and voice attractiveness finding weak positive associations, but small effect sizes. In this study, we empirically investigate the correlation between different modalities of attractiveness in men and women in the largest sample to date (N = 881 ratings). For men, we find no correlations between modalities of attractiveness. However, for women we find odor, face, and voice attractiveness are weakly correlated. Moreover, a general attractiveness factor (i.e., a common underlying variable) modestly contributed to the observed correlations between modality-specific attractiveness judgments, providing some evidence for the redundancy hypothesis.

The caregiver's touch behavior during early infancy is linked to multiple developmental outcomes. However, social touch remains a challenging construct to operationalize, and although observational tools have been a gold standard for measuring touch in caregiver-infant interactions, no systematic review has been conducted before. We followed the PRISMA guidelines and reviewed the literature to describe and classify the main characteristics of the available observational instruments. Of the 3042 publications found, we selected 45 that included an observational measure, and from those we identified 12 instruments. Most of the studies were of infants younger than six months of age and assessed touch in two laboratory tasks: face-to-face interaction and still-face procedure. We identified three approaches for evaluating the caregiver's touch behavior: strictly observational (the observable touch behavior), functional (the functional role of the touch behavior), or mixed (a combination of the previous two). Half of the instruments were classified as functional, 25% as strictly observational, and 25% as mixed. The lack of conceptual and operational uniformity and consistency between instruments is discussed.

The complexity of the habitat refers to its physical geometry, which includes abiotic and biotic elements. Habitat complexity is important because it allows more species to coexist and, consequently, more interactions to be established among them. The complexity of the habitat links the physical structure of the enclosure to the biological interactions, which occur within its limits. Enclosure complexity should vary temporally, to be able to influence the animals in different ways, depending on the period of the day and season and throughout the year. In the present paper, we discuss how habitat complexity is important, and how it can positively influence the physical and mental states of zoo animals. We show how habitat complexity can ultimately affect educational projects. Finally, we discuss how we can add complexity to enclosures and, thus, make the lives of animals more interesting and functional.

Human olfaction can be extraordinarily sensitive, and its most common assessment method is odor identification (OID), where everyday odors are matched to word labels in a multiple-choice format. However, many older persons are unable to identify familiar odors, a deficit that is associated with the risk of future dementia and mortality. The underlying processes subserving OID in older adults are poorly understood. Here, we analyzed error patterns in OID to test whether errors could be explained by perceptual and/or semantic similarities among the response alternatives. We investigated the OID response patterns in a large, population-based sample of older adults in Sweden (n = 2479; age 60-100 years). Olfaction was assessed by a 'Sniffin ́ TOM OID test with 16 odors; each trial involved matching a target odor to a correct label among three distractors. We analyzed the pattern of misidentifications, and the results showed that some distractors were more frequently selected than others, suggesting cognitive or perceptual factors may be present. Relatedly, we conducted a large online survey of older adults (n = 959, age 60-90 years) who were asked to imagine and rate the perceptual similarity of the target odors and the three corresponding distractors (e.g. "How similar are these smells: apple and mint?"). We then used data from the Swedish web corpus and the Word2Vec neural network algorithm to quantify the semantic association strength between the labels of each target odor and its three distractors. These data sources were used to predict odor identification errors. We found that the error patterns were partly explained by both the semantic similarity between target-distractor pairs, and the imagined perceptual similarity of the target-distractor pair. Both factors had, however, a diminished prediction in older ages, as responses became gradually less systematic. In sum, our results suggest that OID tests not only reflect olfactory perception, but also likely involve the mental processing of odor-semantic associations. This may be the reason why these tests are useful in predicting dementia onset. Our insights into olfactory-language interactions could be harnessed to develop new olfactory tests that are tailored for specific clinical purposes.

Floral scent plays a crucial role in the reproductive process of many plants. Humans have been fascinated by floral scents throughout history, and have transported and traded floral scent products for which they have found multiple uses, such as in food additives, hygiene and perfume products, and medicines. Yet the scientific study of how plants synthesize floral scent compounds began later than studies on most other major plant metabolites, and the first report of the characterization of an enzyme responsible for the synthesis of a floral scent compound, namely linalool in Clarkia breweri, a California annual, appeared in 1994. In the almost 30 years since, enzymes and genes involved in the synthesis of hundreds of scent compounds from multiple plant species have been described. This review recapitulates this history and describes the major findings relating to the various aspects of floral scent biosynthesis and emission, including genes and enzymes and their evolution, storage and emission of scent volatiles, and the regulation of the biochemical processes.

Disorders of the sense of smell have received greater attention because of the frequency with which they occur as a symptom of SARS-CoV-2 infection. Olfactory dysfunction can lead to profound reduction in quality of life and may arise from many different causes.

A selective literature review was conducted with consideration of the current version of the guideline issued by the Association of the Scientific Medical Societies in Germany.

The cornerstones of diagnosis are the relevant medical history and psychophysical testing of olfactory function using standardized validated tests. Modern treatment strategies are oriented on the cause of the dysfunction. While treatment of the underlying inflammation takes precedence in patients with sinunasal dysosmia, olfactory training is the primary treatment option for other forms of the disorder. The prognosis is determined not only by the cause of the olfactory dysfunction and the patient's age, but also by the olfactory performance as measured at the time of diagnosis.

Options for the treatment of olfactory dysfunction are available but limited, depending on the cause. It is therefore important to carry out a detailed diagnostic work-up and keep the patient informed of the expected course and prognosis.

Throughout the animal kingdom, our two chemical senses, olfaction and gustation, are defined by two primary factors: genomic architecture of the organisms and their living environment. During the past three years of the global COVID-19 pandemic, these two sensory modalities have drawn much attention at the basic science and clinical levels because of the strong association of olfactory and gustatory dysfunction with viral infection. Loss of our sense of smell alone, or together with a loss of taste, has emerged as a reliable indicator of COVID-19 infection. Previously, similar dysfunctions have been detected in a large cohort of patients with chronic conditions. The research focus remains on understanding the persistence of olfactory and gustatory disturbances in the post-infection phase, especially in cases with long-term effect of infection (long COVID). Also, both sensory modalities show consistent age-related decline in studies aimed to understand the pathology of neurodegenerative conditions. Some studies using classical model organisms show an impact on neural structure and behavior in offspring as an outcome of parental olfactory experience. The methylation status of specific odorant receptors, activated in parents, is passed on to the offspring. Furthermore, experimental evidence indicates an inverse correlation of gustatory and olfactory abilities with obesity. Such diverse lines of evidence emerging from basic and clinical research studies indicate a complex interplay of genetic factors, evolutionary forces, and epigenetic alterations. Environmental factors that regulate gustation and olfaction could induce epigenetic modulation. However, in turn, such modulation leads to variable effects depending on genetic makeup and physiological status. Therefore, a layered regulatory hierarchy remains active and is passed on to multiple generations. In the present review, we attempt to understand the experimental evidence that indicates variable regulatory mechanisms through multilayered and cross-reacting pathways. Our analytical approach will add to enhancement of prevailing therapeutic interventions and bring to the forefront the significance of chemosensory modalities for the evaluation and maintenance of long-term health.

The sense of smell has been underestimated for a long time in humans. It has been brought to the fore by its sudden disappearance during the Covid-19 pandemic of which anosmia (complete loss of smell) is one of the major symptoms. However, respiratory viruses have long been associated with smell disorders, 25% of which are linked to a viral infection. Olfaction begins in the nose within the olfactory epithelium which has the particularity of containing neurons in direct contact with the environment. Several respiratory viruses are known for their replicative capacity within this epithelium. This is particularly the case for the flu virus (influenza) and bronchiolitis (respiratory syncytial virus) but their tropism for this tissue is much lower than SARS-CoV-2. The understanding of the SARS-CoV-2 pathophysiology in the nasal cavity makes it possible to reveal part of the links between viral infection and olfactory disorders.

Olfaction is tightly regulated by internal status such as hunger level. The influence of fasted and fed states on olfactory sensitivity in humans has reached mixed results. This study aims to systematically review, integrate and meta-analyze evidence of the impact of fasting on olfactory sensitivity in humans and to explore the impact of potential moderators.

Electronic databases (PubMed, PsycINFO, Web of Science, COCHRANE and Ovid) were searched for studies with human participants investigating the effect of fasting on olfactory sensitivity. Studies were included in the review if they measured odor threshold both at fasted and sated status. The data extraction was determined based on the change in odor threshold from the fasted state to the fed state. Meta-analysis was conducted using a random-effect model to estimate the standardized mean difference transformed olfactory sensitivity change between fasted and fed states with 95% confidence interval (CI).

Thirteen studies (12 articles) were included in the meta-analysis with a total of 550 participants. Olfactory sensitivity was higher in the fasted state compared to the fed state (SMD = -0.251, 95% CI = -0.426, -0.075, Z = -2.804, p = 0.005). Separated analyses for food and non-food odors revealed a significant elevated sensitivity to non-food odors during the fasted state compared to the fed state. The meta-regression analysis revealed that fasting time positively moderate the increased olfactory sensitivity from the fasted to fed states (β = -0.013, 95% CI = -0.023, -0.002, p = 0.016).

Fasting improves human olfactory sensitivity to non-food odors, and this effect increases with longer fasting time. Future research design on olfactory sensitivity should take both the fasted state and fasting period of the participants into consideration.

Epilepsy is a common and serious neurological disorder, to which a high proportion of patients continue to be considered "drug-resistant", despite the availability of a host of anti-seizure drugs. Investigation into new treatment strategies is therefore of great importance. One such strategy is the use of the nose to deliver drugs directly to the brain with the help of pharmaceutical formulation to overcome the physical challenges presented by this route. The following review explores intranasal delivery of anti-seizure drugs, covering the link between the nose and seizures, pathways from the nose to the brain, current formulations in clinical use, animal seizure models and their proposed application in studying intranasal treatments, and a critical discussion of relevant pre-clinical studies in the literature.