Olfactory function after mild traumatic brain injury in children-a longitudinal case control study.

The prevalence of posttraumatic olfactory dysfunction in children after mild traumatic brain injury ranges from 3 to 58%, with potential factors influencing this variation, including traumatic brain injury severity and assessment methods. This prospective longitudinal study examines the association between mild traumatic brain injury and olfactory dysfunction in children. Seventy-five pediatric patients with mild traumatic brain injury and an age-matched healthy control group were enrolled. Olfactory function was assessed using the Sniffin' Sticks battery, which focuses on olfactory threshold and odor identification. The study found that children with mild traumatic brain injury had impaired olfactory function compared with healthy controls, particularly in olfactory threshold scores. The prevalence of olfactory dysfunction in the patient group was 33% and persisted for 1 yr. No significant association was found between traumatic brain injury symptoms (e.g. amnesia, loss of consciousness) and olfactory dysfunction. The study highlights the importance of assessing olfactory function in children after mild traumatic brain injury, given its potential impact on daily life. Although most olfactory dysfunction appears transient, long-term follow-up is essential to fully understand the recovery process. The findings add valuable insights to the limited literature on this topic and urge the inclusion of olfactory assessments in the management of pediatric mild traumatic brain injury.

Localized Expression of Olfactory Receptor Genes in the Olfactory Organ of Common Minke Whales.

Baleen whales (Mysticeti) possess the necessary anatomical structures and genetic elements for olfaction. Nevertheless, the olfactory receptor gene (OR) repertoire has undergone substantial degeneration in the cetacean lineage following the divergence of the Artiodactyla and Cetacea. The functionality of highly degenerated mysticete ORs within their olfactory epithelium remains unknown. In this study, we extracted total RNA from the nasal mucosae of common minke whales (Balaenoptera acutorostrata) to investigate ORs' localized expression. All three sections of the mucosae examined in the nasal chamber displayed comparable histological structure. However, the posterior portion of the frontoturbinal region exhibited notably high OR expression. Neither the olfactory bulb nor the external skin exhibited the expression of these genes. Although this species possesses four intact non-class-2 ORs, all the ORs expressed in the nasal mucosae belong to class-2, implying the loss of aversion to specific odorants. These anatomical and genomic analyses suggest that ORs are still responsible for olfaction within the nasal region of baleen whales, enabling them to detect desirable scents such as prey and potential mating partners.

Smelling TNT: Trends of the Terminal Nerve.

There is very little knowledge regarding the terminal nerve, from its implications in the involvement and pathogenesis of certain conditions, to its embryological origin. With this review, we try to summarize the most important evidence on the terminal nerve, aiming to clarify its anatomy and the various functions attributed to it, to better interpret its potential involvement in pathological processes. Recent studies have also suggested its potential role in the control of human reproductive functions and behaviors. It has been hypothesized that it plays a role in the unconscious perception of specific odors that influence autonomic and reproductive hormonal systems through the hypothalamic-pituitary-gonadal axis. We used the PubMed database and found different articles which were then selected independently by three authors. We found 166 articles, of which, after careful selection, only 21 were analyzed. The terminal nerve was always thought to be unimportant in our body. It was well studied in different types of animals, but few studies have been completed in humans. For this reason, its function remains unknown. Studies suggest a possible implication in olfaction due to the anatomical proximity with the olfactive nerve. Others suggest a more important role in reproduction and sexual behaviors. New emerging information suggests a possible role in Kallmann syndrome and COVID-19.

Cognitive impairment, neurodegenerative disorders, and olfactory impairment: A literature review.

<br><b>Introduction:</b> The early detection and diagnosis of dementia are of key importance in treatment, slowing disease progression, or suppressing symptoms. The possible role of changes in the sense of smell is considered with regard to potential markers for early detection of Alzheimer's disease (AD).</br> <br><b>Materials and methods:</b> A literature search was conducted using the electronic databases PubMed, Scopus, and Web of Science between May 30, 2022 and August 2, 2022. The term "dementia" was searched with keyword combinations related to olfaction.</br> <br><b>Results:</b> A total of 1,288 records were identified through the database search. Of these articles, 49 were ultimately included in the analysis. The results showed the potential role of changes in the sense of smell as potential biomarkers for early detection of AD. Multiple studies have shown that olfactory impairment may be observed in patients with AD, PD, MCI, or other types of dementia. Even though smell tests are able to detect olfactory loss caused by neurodegenerative diseases, they cannot reliably distinguish between certain diseases.</br> <br><b>Conclusions:</b> In individuals with cognitive impairment or neurodegenerative diseases, olfactory assessment has repeatedly been reported to be used for early diagnosis, but not for differential diagnosis.</br>.

The Olfactory Trail of Neurodegenerative Diseases.

Alterations in olfactory functions are proposed as possible early biomarkers of neurodegenerative diseases. Parkinson's and Alzheimer's diseases manifest olfactory dysfunction as a symptom, which is worth mentioning. The alterations do not occur in all patients, but they can serve to rule out neurodegenerative pathologies that are not associated with small deficits. Several prevalent neurodegenerative conditions, including impaired smell, arise in the early stages of Parkinson's and Alzheimer's diseases, presenting an attractive prospect as a snitch for early diagnosis. This review covers the current knowledge on the link between olfactory deficits and Parkinson's and Alzheimer's diseases. The review also covers the emergence of olfactory receptors as actors in the pathophysiology of these diseases. Olfactory receptors are not exclusively expressed in olfactory sensory neurons. Olfactory receptors are widespread in the human body; they are expressed, among others, in the testicles, lungs, intestines, kidneys, skin, heart, and blood cells. Although information on these ectopically expressed olfactory receptors is limited, they appear to be involved in cell recognition, migration, proliferation, wound healing, apoptosis, and exocytosis. Regarding expression in non-chemosensory regions of the central nervous system (CNS), future research should address the role, in both the glia and neurons, of olfactory receptors. Here, we review the limited but relevant information on the altered expression of olfactory receptor genes in Parkinson's and Alzheimer's diseases. By unraveling how olfactory receptor activation is involved in neurodegeneration and identifying links between olfactory structures and neuronal death, valuable information could be gained for early diagnosis and intervention strategies in neurodegenerative diseases.

The trilogy of human musk receptors: linking receptor activation, genotype, and sensory perception.

The scent of musk plays a unique role in the history of perfumery. Musk odorants comprise 6 diverse chemical classes and perception differences in strength and quality among human panelists have long puzzled the field of olfaction research. Three odorant receptors (OR) had recently been described for musk odorants: OR5AN1, OR1N2, and OR5A2. High functional expression of the difficult-to-express human OR5A2 was achieved by a modification of the C-terminal domain and the link between sensory perception and receptor activation for the trilogy of these receptors and their key genetic variants was investigated: All 3 receptors detect only musky smelling compounds among 440 commercial fragrance compounds. OR5A2 is the key receptor for the classes of polycyclic and linear musks and for most macrocylic lactones. A single P172L substitution reduces the sensitivity of OR5A2 by around 50-fold. In parallel, human panelists homozygous for this mutation have around 40-60-fold higher sensory detection threshold for selective OR5A2 ligands. For macrocyclic lactones, OR5A2 could further be proven as the key OR by a strong correlation between in vitro activation and the sensory detection threshold in vivo. OR5AN1 is the dominant receptor for the perception of macrocyclic ketones such as muscone and some nitromusks, as panelists with a mutant OR5A2 are still equally sensitive to these ligands. Finally, OR1N2 appears to be an additional receptor involved in the perception of the natural (E)-ambrettolide. This study for the first time links OR activation to sensory perception and genetic polymorphisms for this unique class of odorants.

Post-COVID syndrome: analysis of the prevalence of chemosensory dysfunction and predictive factors of recovery in COVID-19 long-haulers in Jordan.

OBJECTIVE: One of the major concerns of the post-COVID-19 era is elucidating and addressing the long-term complications of COVID-19. SUBJECTS AND METHODS: A web-based questionnaire was distributed in Jordan to assess the prevalence and recovery from chemosensory dysfunction among COVID-19 long-haulers in Jordan. RESULTS: A total of 611 respondents complained of chemosensory dysfunction (age range = 18-68 years), and the majority of the respondents were female (88.4%). Parosmia was the most prevalent olfactory dysfunction reported (n = 337, 33.3%), and parageusia was the most frequently reported gustatory dysfunction (n = 239, 36.4%). Medications were not reported to be associated with a better perception of smell or taste by nearly half of those who had been treated (n = 146, 46.1%). Among participants who had received olfactory rehabilitation/training (n = 215, 35.2%), 43.7% (n = 94) reported modest improvement, with the most frequently helpful scents being coffee (n = 80, 24.8%), aromatic oils (n = 74, 23%), and perfumes/colognes (n = 73, 22.7%). Age was found to have a significant negative correlation with complete recovery. In addition, age (p < .05), anosmia (p < .001), hyperosmia (p < .001), ageusia (p < .05), and duration of olfactory dysfunction (p < .001) were all independent predictors of complete recovery. CONCLUSIONS: Chemosensory dysfunctions are largely subjective; therefore, more objective examinations are required to draw more definite conclusions.

Sociosexual interactions: A clock synchronized by smell.

While the daily rhythmicity of organisms is entrained by several cues, light is thought to be the strongest signal. Surprisingly, a new study in a moth shows that olfactory communication can be even more powerful for synchronization, and, at least to some extent, works across related species.

Subtle morphological changes in the visual and antennal sensory system of bees and wasps across an urbanisation gradient.

Increased temperature and fragmentation of green spaces in urban areas could drive variations in functional traits of insects. Such morphological shifts may occur for sensory systems, which were previously reported to be prone to change with habitat characteristics in non-urban contexts. Here, we measured traits related to the visual and antennal sensory systems in the bees Halictus scabiosae and Osmia cornuta and the wasp Polistes dominula along an urbanisation gradient within Milan (Italy). We hypothesised that fragmentation could filter for better visual properties, and that higher temperature could filter for fewer thermoreceptors and more olfactory hairs. While controlling for body size, results show subtle but appreciable responses to urbanisation in one or more traits in all species, though not always supporting our hypotheses. O. cornuta shows marginally higher ommatidia density and smaller ommatidia diameter (associated with better visual resolution) in more fragmented sites, as well as marginally fewer thermoreceptors in hotter sites, in agreement with our two predictions. On the other hand, H. scabiosae has marginally smaller antennae and P. dominula has smaller eyes at warmer locations, and the wasp also has smaller antennae and 9th flagellomeres in more fragmented areas. Perhaps higher temperatures accelerate development of sensory system at higher speed than the rest of body in these two species. Our results represent the first evidence of urbanisation effects on the visual and antennal sensory systems of bees and wasps and underline how such effects may involve a much broader bouquet of traits then previously observed.

CD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators.

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian olfactory receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.

Distinct information conveyed to the olfactory bulb by feedforward input from the nose and feedback from the cortex.

Sensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical feedback projections numerically match sensory inputs. To unravel information carried by these two streams, we imaged the activity of olfactory sensory neurons (OSNs) and cortical axons in the mouse OB using calcium indicators, multiphoton microscopy, and diverse olfactory stimuli. Here, we show that odorant mixtures of increasing complexity evoke progressively denser OSN activity, yet cortical feedback activity is of similar sparsity for all stimuli. Also, representations of complex mixtures are similar in OSNs but are decorrelated in cortical axons. While OSN responses to increasing odorant concentrations exhibit a sigmoidal relationship, cortical axonal responses are complex and nonmonotonic, which can be explained by a model with activity-dependent feedback inhibition in the cortex. Our study indicates that early-stage olfactory circuits have access to local feedforward signals and global, efficiently formatted information about odor scenes through cortical feedback.

Epigenetic programming of stochastic olfactory receptor choice.

The mammalian sense of smell relies upon a vast array of receptor proteins to detect odorant compounds present in the environment. The proper deployment of these receptor proteins in olfactory sensory neurons is orchestrated by a suite of epigenetic processes that remodel the olfactory genes in differentiating neuronal progenitors. The goal of this review is to elucidate the central role of gene regulatory processes acting in neuronal progenitors of olfactory sensory neurons that lead to a singular expression of an odorant receptor in mature olfactory sensory neurons. We begin by describing the principal features of odorant receptor gene expression in mature olfactory sensory neurons. Next, we delineate our current understanding of how these features emerge from multiple gene regulatory mechanisms acting in neuronal progenitors. Finally, we close by discussing the key gaps in our understanding of how these regulatory mechanisms work and how they interact with each other over the course of differentiation.

What do brain oscillations tell about the human sense of smell?

Brain activity may manifest itself as oscillations which are repetitive rhythms of neuronal firing. These local field potentials can be measured via intracranial electroencephalography (iEEG). This review focuses on iEEG used to map human brain structures involved in olfaction. After presenting the methodology of the review, a summary of the brain structures involved in olfaction is given, followed by a review of the literature on human olfactory oscillations in different contexts. A single case is provided as an illustration of the olfactory oscillations. Overall, the timing and sequence of oscillations found in the different structures of the olfactory system seem to play an important role for olfactory perception.

Remote olfactory assessment using the NIH Toolbox Odor Identification test and the brain health registry.

BACKGROUND: Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. To realistically enable population-level measurements of olfaction, validated olfaction tests must be capable of being administered outside the research laboratory and clinical setting. AIM: The purpose of this study was to determine the feasibility of remotely testing olfactory performance using a test that was developed with funding from the National Institutes of Health as part of a ready-to-use, non-proprietary set of measurements useful for epidemiologic studies (NIH Toolbox Odor ID Test). MATERIALS AND METHODS: Eligible participants older than 39 years and active (within 6 months) in the Brain Health Registry (BHR), an online cognitive assessment platform which connects participants with researchers, were recruited for this study. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses. Data obtained from subjects who performed the test at home was compared to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting and validated against the Smell Identification Test. The age-range and composition of the population ensured we had the ability to observe both age-related decline and gender-related deficits in olfactory ability, as shown in the experimental setting. RESULTS: We observed that age-associated olfactory decline and gender-associated performance was comparable to performance on the administered test. Self-administration of this test showed the age-related loss in olfactory acuity, F(4, 1156)=14.564, p<.0001 as well as higher accuracy for women compared to men after controlling for participants' age, F(1, 1160) = 22.953, p <.0001. The effect size calculated as Hedge's g, was 0.41. CONCLUSION: These results indicate that the NIH Toolbox Odor ID Test is an appropriate instrument for self-administered assessment of olfactory performance. The ability to self-administer an inexpensive olfactory test increases its utility for inclusion in longitudinal epidemiological studies and when in-person testing is not feasible.

Olfactory self-recognition in two species of snake.

Mark tests, in which an animal uses a mirror to locate and examine an otherwise unnoticeable mark on its own body, are commonly used to assess self-recognition, which may have implications for self-awareness. Recently, several olfactory-reliant species have appeared to pass odour-based versions of the mark test, though it has never been attempted in reptiles. We conducted an odour-based mark test on two species of snakes, Eastern gartersnakes and ball pythons, with widely divergent ecologies (i.e. terrestrial foragers that communally brumate versus semi-arboreal ambush predators that do not). We find that gartersnakes, but not ball pythons, pass the test, and a range of control tests suggest this is based on self-recognition. Gartersnakes are more social than ball pythons, supporting recent suggestions that social species are more likely to self-recognize. These results open the door to examination of the ecology of self-recognition, and suggest that this ability may evolve in response to species-specific ecological challenges, some of which may align with complexity of social structures.

Differential connectivity of the posterior piriform cortex in Parkinson's disease and postviral olfactory dysfunction: an fMRI study.

Olfactory dysfunction is a common feature of both postviral upper respiratory tract infections (PV) and idiopathic Parkinson's disease (PD). Our aim was to investigate potential differences in the connectivity of the posterior piriform cortex, a major component of the olfactory cortex, between PV and PD patients. Fifteen healthy controls (median age 66 years, 9 men), 15 PV (median age 63 years, 7 men) and 14 PD patients (median age 70 years, 9 men) were examined with task-based olfactory fMRI, including two odors: peach and fish. fMRI data were analyzed with the co-activation pattern (CAP) toolbox, which allows a dynamic temporal assessment of posterior piriform cortex (PPC) connectivity. CAP analysis revealed 2 distinct brain networks interacting with the PPC. The first network included regions related to emotion recognition and attention, such as the anterior cingulate and the middle frontal gyri. The occurrences of this network were significantly fewer in PD patients compared to healthy controls (p = 0.023), with no significant differences among PV patients and the other groups. The second network revealed a dissociation between the olfactory cortex (piriform and entorhinal cortices), the anterior cingulate gyrus and the middle frontal gyri. This second network was significantly more active during the latter part of the stimulation, across all groups, possibly due to habituation. Our study shows how the PPC interacts with areas that regulate higher order processing and how this network is substantially affected in PD. Our findings also suggest that olfactory habituation is independent of disease.

Value-related learning in the olfactory bulb occurs through pathway-dependent perisomatic inhibition of mitral cells.

Associating values to environmental cues is a critical aspect of learning from experiences, allowing animals to predict and maximise future rewards. Value-related signals in the brain were once considered a property of higher sensory regions, but their wide distribution across many brain regions is increasingly recognised. Here, we investigate how reward-related signals begin to be incorporated, mechanistically, at the earliest stage of olfactory processing, namely, in the olfactory bulb. In head-fixed mice performing Go/No-Go discrimination of closely related olfactory mixtures, rewarded odours evoke widespread inhibition in one class of output neurons, that is, in mitral cells but not tufted cells. The temporal characteristics of this reward-related inhibition suggest it is odour-driven, but it is also context-dependent since it is absent during pseudo-conditioning and pharmacological silencing of the piriform cortex. Further, the reward-related modulation is present in the somata but not in the apical dendritic tuft of mitral cells, suggesting an involvement of circuit components located deep in the olfactory bulb. Depth-resolved imaging from granule cell dendritic gemmules suggests that granule cells that target mitral cells receive a reward-related extrinsic drive. Thus, our study supports the notion that value-related modulation of olfactory signals is a characteristic of olfactory processing in the primary olfactory area and narrows down the possible underlying mechanisms to deeper circuit components that contact mitral cells perisomatically.

3D multi-robot olfaction in naturally ventilated indoor environments: Locating a time-varying source at unknown heights.

Source localization is significant for mitigating indoor air pollution and safeguarding the well-being and safety of occupants. While most study focuses on mechanical ventilation and static sources, this study explores the less-explored domain of locating time-varying sources in naturally ventilated spaces. We have developed an innovative 3D localization system that adjusts to varying heights, significantly enhancing capabilities beyond traditional fixed-height 2D systems. To ensure consistency in experimental conditions, we conducted comparative analyses of 2D and 3D methods, using a swinging fan to simulate natural ventilation. Our findings reveal a substantial disparity in performance: the 2D method had a success rate below 46.7% in cases of height mismatches, while our 3D methods consistently achieved success rates above 66.7%, demonstrating their superior effectiveness in complex environments. Furthermore, we validated the 3D strategies in real naturally ventilated settings, confirming their wider applicability. This research extends the scope of indoor source localization and offers valuable insights and strategies for more effective pollution control.

Circuit formation and sensory perception in the mouse olfactory system.

In the mouse olfactory system, odor information is converted to a topographic map of activated glomeruli in the olfactory bulb (OB). Although the arrangement of glomeruli is genetically determined, the glomerular structure is plastic and can be modified by environmental stimuli. If the pups are exposed to a particular odorant, responding glomeruli become larger recruiting the dendrites of connecting projection neurons and interneurons. This imprinting not only increases the sensitivity to the exposed odor, but also imposes the positive quality on imprinted memory. External odor information represented as an odor map in the OB is transmitted to the olfactory cortex (OC) and amygdala for decision making to elicit emotional and behavioral outputs using two distinct neural pathways, innate and learned. Innate olfactory circuits start to work right after birth, whereas learned circuits become functional later on. In this paper, the recent progress will be summarized in the study of olfactory circuit formation and odor perception in mice. We will also propose new hypotheses on the timing and gating of olfactory circuit activity in relation to the respiration cycle.

An observational study of olfactory functions in total laryngectomees.

OBJECTIVE: To evaluate the olfactory acuity and quality of life in patients who have undergone total laryngectomy. The study also aims to identify any specific patient-related risk factors linked to worse olfactory outcomes. METHODS: This is a prospective cross-sectional study conducted at the University Malaya Medical Centre. A total of 30 patients who have undergone total laryngectomy were assessed objectively using the Sniffin' Sticks test and compared against normal age-matched Malaysians. Subsequently, they also filled out the modified Questionnaire on Olfactory Disorders. Correlations of patient demographics, disease and treatment variables against olfactory outcomes were conducted. RESULTS: All subjects suffered olfactory impairment, with 66.7% of them being anosmic after total laryngectomy. The Sniffin' Sticks test demonstrated a statistically significant difference between laryngectomees and the normal age-matched Malaysian population in all three subtests for odor threshold, discrimination and identification. 37% of patients developed olfactory adaptive methods, which resulted in higher olfactory scores and a better quality of life. There were no patient demographics, disease or treatment variables associated with a poorer olfactory outcome identified. CONCLUSION: Olfactory impairment should not be overlooked among patients after total laryngectomy. Although as many as a third of patients developed some sort of olfactory adaptive behavior, early rehabilitation should be integrated into the multidisciplinary rehabilitation program after total laryngectomy.