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Rhinology Dec 2023Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is...
BACKGROUND
Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is unclear. Dupilumab improves sense of smell and radiographic severity of sinus disease in patients with CRSwNP. We investigated the relationship of sinus opacification severity and loci to olfactory impairment and dupilumab efficacy in patients with CRSwNP from the SINUS-24/SINUS-52 (NCT02912468/NCT02898454) studies.
METHODS
Sinus opacification was evaluated using the Lund-Mackay computed tomography (LMK-CT) score and sense of smell using patient-reported loss of smell (LoS) score, University of Pennsylvania Smell Identification Test (UPSIT) score and the 22-item Sino-Nasal Outcome Test (SNOT-22) smell/taste item.
RESULTS
At baseline, 95% of patients (688/724) had impaired sense of smell and opacification was extensive across all sinuses. Greater olfactory impairment was associated with greater opacification, especially in the ethmoid, sphenoid and frontal sinuses. At Week 24, reductions in LMK-CT total score and ethmoid and sphenoid sinus scores with dupilumab were weakly correlated with improvements in sense of smell assessed by LoS, UPSIT and SNOT-22 smell/taste item. More dupilumab than placebo patients achieved clinically meaningful improvement in LMK-CT total score at Week 24 and Week 52.
CONCLUSION
Radiographic disease severity on imaging was associated with smell outcomes in this cohort. Opacification of the ethmoid, sphenoid and frontal sinuses was associated with severe smell loss. These data suggest that dupilumab effects on smell may be partly mediated through reduced sinus inflammation.
Topics: Humans; Nasal Polyps; Smell; Rhinitis; Sinusitis; Chronic Disease; Olfaction Disorders; Frontal Sinus
PubMed: 37453138
DOI: 10.4193/Rhin22.220 -
Clinical Genetics Apr 2024An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic,...
An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic, or isolated congenital anosmia (ICA). Despite the significant impact of olfaction for our quality of life, the underlying causes of ICA remain largely unknown. Using whole exome sequencing (WES) in 10 families and 141 individuals with ICA, we identified a candidate list of 162 rare, segregating, deleterious variants in 158 genes. We confirmed the involvement of CNGA2, a previously implicated ICA gene that is an essential component of the olfactory transduction pathway. Furthermore, we found a loss-of-function variant in SREK1IP1 from the family gene candidate list, which was also observed in 5% of individuals in an additional non-family cohort with ICA. Although SREK1IP1 has not been previously associated with olfaction, its role in zinc ion binding suggests a potential influence on olfactory signaling. This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.
Topics: Humans; Quality of Life; Olfaction Disorders; Mutation; Signal Transduction; Smell; Cyclic Nucleotide-Gated Cation Channels
PubMed: 38148624
DOI: 10.1111/cge.14470 -
Integrative and Comparative Biology Aug 2023Pheromones are chemical signals that facilitate communication between animals, and most animals use pheromones for reproduction and other forms of social behavior. The... (Review)
Review
Pheromones are chemical signals that facilitate communication between animals, and most animals use pheromones for reproduction and other forms of social behavior. The identification of key ligands and olfactory receptors used for pheromonal communication provides insight into the sensory processing of these important cues. An individual's responses to pheromones can be plastic, as physiological status modulates behavioral outputs. In this review, we outline the mechanisms for pheromone sensation and highlight physiological mechanisms that modify pheromone-guided behavior. We focus on hormones, which regulate pheromonal communication across vertebrates including fish, amphibians, and rodents. This regulation may occur in peripheral olfactory organs and the brain, but the mechanisms remain unclear. While this review centers on research in fish, we will discuss other systems to provide insight into how hormonal mechanisms function across taxa.
Topics: Animals; Pheromones; Smell; Hormones; Fishes; Perception
PubMed: 37263784
DOI: 10.1093/icb/icad049 -
Proceedings of the National Academy of... Aug 2023Long-range olfactory search is an extremely difficult task in view of the sparsity of odor signals that are available to the searcher and the complex encoding of the...
Long-range olfactory search is an extremely difficult task in view of the sparsity of odor signals that are available to the searcher and the complex encoding of the information about the source location. Current algorithmic approaches typically require a continuous memory space, sometimes of large dimensionality, which may hamper their optimization and often obscure their interpretation. Here, we show how finite-state controllers with a small set of discrete memory states are expressive enough to display rich, time-extended behavioral modules that resemble the ones observed in living organisms. Finite-state controllers optimized for olfactory search have an immediate interpretation in terms of approximate clocks and coarse-grained spatial maps, suggesting connections with neural models of search behavior.
Topics: Smell; Odorants
PubMed: 37579168
DOI: 10.1073/pnas.2304230120 -
Auris, Nasus, Larynx Aug 2023One of the unique symptoms of COVID-19 is chemosensory dysfunction. Almost three years since the beginning of the pandemic of COVID-19, there have been many studies on... (Review)
Review
One of the unique symptoms of COVID-19 is chemosensory dysfunction. Almost three years since the beginning of the pandemic of COVID-19, there have been many studies on the symptoms, progress, and possible causes, and also studies on methods that may facilitate recovery of the senses. Studies have shown that some people recover their senses even within a couple of weeks whereas there are other patients that fail to recover chemosensory functions fully for several months and some never fully recover. Here we summarize the symptoms and the progress, and then review the papers on the causation as well as the treatments that may help facilitate the recovery of the symptoms. Depending on the differences in the levels of severity and the locations where the main pathological venues are, what is most effective in facilitating recovery can vary largely across patients and thus may require individualized strategies for each patient. The goal of this paper is to provide some thoughts on these choices depending on the differences in the causes and severity.
Topics: Humans; COVID-19; SARS-CoV-2; Olfaction Disorders; Smell; Pandemics
PubMed: 36529610
DOI: 10.1016/j.anl.2022.12.002 -
Cell Reports Dec 2023Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial...
Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial short-axon cells in the olfactory bulb release both dopamine and γ-aminobutyric acid (GABA), yet the specific targets of these neurotransmitters and their respective roles in olfaction have remained unknown. Here, we implement intersectional genetics in mice to selectively block GABA or dopamine release from superficial short-axon cells to identify their distinct cellular targets, impact on circuit function, and behavioral contribution of each neurotransmitter toward olfactory behaviors. We provide functional and anatomical evidence for divergent superficial short-axon cell signaling onto downstream neurons to shape patterns of mitral cell firing that contribute to olfactory-related behaviors.
Topics: Mice; Animals; Olfactory Bulb; Smell; Dopamine; Interneurons; gamma-Aminobutyric Acid; Neurotransmitter Agents
PubMed: 37980561
DOI: 10.1016/j.celrep.2023.113471 -
Neuroscience and Biobehavioral Reviews Aug 2023Infant survival relies on rapid identification, remembering and behavioral responsiveness to caregivers' sensory cues. While neural circuits supporting infant attachment... (Review)
Review
Infant survival relies on rapid identification, remembering and behavioral responsiveness to caregivers' sensory cues. While neural circuits supporting infant attachment learning have largely remained elusive in children, use of invasive techniques has uncovered some of its features in rodents. During a 10-day sensitive period from birth, newborn rodents associate maternal odors with maternal pleasant or noxious thermo-tactile stimulation, which gives rise to a preference and approach behavior towards these odors, and blockade of avoidance learning. Here we review the neural circuitry supporting this neonatal odor learning, unique compared to adults, focusing specifically on the early roles of neurotransmitters such as glutamate, GABA (Gamma-AminoButyric Acid), serotonin, dopamine and norepinephrine, in the olfactory bulb, the anterior piriform cortex and amygdala. The review highlights the importance of deepening our knowledge of age-specific infant brain neurotransmitters and behavioral functioning that can be translated to improve the well-being of children during typical development and aid in treatment during atypical development in childhood clinical practice, and the care during rearing of domestic animals.
Topics: Rats; Animals; Animals, Newborn; Rats, Long-Evans; Olfactory Bulb; Odorants; Avoidance Learning; Neurotransmitter Agents; Smell
PubMed: 37257712
DOI: 10.1016/j.neubiorev.2023.105249 -
Acta Physiologica (Oxford, England) Sep 2023General anesthesia can induce cognitive deficits in both humans and rodents, correlating with pathological alterations in the hippocampus. However, whether general...
AIM
General anesthesia can induce cognitive deficits in both humans and rodents, correlating with pathological alterations in the hippocampus. However, whether general anesthesia affects olfactory behaviors remains controversial as clinical studies have produced inconsistent results. Therefore, we aimed to investigate how olfactory behaviors and neuronal activity are affected by isoflurane exposure in adult mice.
METHODS
The olfactory detection test, olfactory sensitivity test, and olfactory preference/avoidance test were used to examine olfactory function. In vivo electrophysiology was performed in awake, head-fixed mice to record single-unit spiking and local field potentials in the olfactory bulb (OB). We also performed patch-clamp recordings of mitral cell activity. For morphological studies, immunofluorescence and Golgi-Cox staining were applied.
RESULTS
Repeated exposure to isoflurane impaired olfactory detection in adult mice. The main olfactory epithelium, the first region exposed to anesthetics, displayed increased proliferation of basal stem cells. In the OB, a crucial hub for olfactory processing, repeated isoflurane exposure increased the odor responses of mitral/tufted cells. Furthermore, the odor-evoked high gamma response was decreased after isoflurane exposure. Whole-cell recordings further indicated that repeated isoflurane exposure increased the excitability of mitral cells, which may be due to weakened inhibitory input in isoflurane-exposed mice. In addition, elevated astrocyte activation and glutamate transporter-1 expression in the OB were observed in isoflurane-exposed mice.
CONCLUSIONS
Our findings indicate that repeated isoflurane exposure impairs olfactory detection by increasing neuronal activity in the OB in adult mice.
Topics: Humans; Mice; Animals; Smell; Olfactory Bulb; Isoflurane; Neurons; Odorants
PubMed: 37330999
DOI: 10.1111/apha.14009 -
Strahlentherapie Und Onkologie : Organ... Oct 2023Patients sometimes report phosphene and phantosmia during radiation therapy (RT). However, the detail features and related factors are not well understood. Our...
PURPOSE
Patients sometimes report phosphene and phantosmia during radiation therapy (RT). However, the detail features and related factors are not well understood. Our prospective study aimed to investigate the characteristics of phantosmias and phosphenes, to identify factors that influence the occurrence, intensity and hedonic (pleasantness/unpleasantness) ratings of such sensations during RT.
METHODS
We included a total of 106 patients (37 women), who underwent RT in regions of the brain, ear, nose, throat (ENT), and other areas of the body for a duration of 43 ± 5 days. Medical history and treatment parameters were collected in a structured medical interview. Olfactory function was measured using the Sniffin' Stick Odor Identification Test at baseline. Phantosmia and phosphene were recorded weekly based on a self-report questionnaire.
RESULTS
There were 37% of the patients experiencing phantosmias, 51% experiencing phosphenes, and 29% simultaneously experiencing both sensations. Phosphenes were typically perceived as a flashily blue, white and/or purple light, phantosmias were typically perceived as a chemical-like, metallic or burnt smell. Younger age (F = 7.81, p < 0.01), radiation in the brain region (χ = 14.05, p = 0.02), absence of taste problems (χ = 10.28, p = 0.01), and proton RT (χ = 10.57, p = 0.01) were related to these abnormal sensations. History of chemical/dust exposure predicted lower intensity (B = -1.52, p = 0.02) and lower unpleasantness (B = 0.49, p = 0.03) of phantosmia. In contrast, disease (tumor) duration (B = 0.11, p < 0.01), food allergy (B = 2.77, p < 0.01), and epilepsy (B = -1.50, p = 0.02) influence phosphenes intensity. Analgesics intake predicted a higher pleasantness of the phosphenes (B = 0.47, p < 0.01).
CONCLUSIONS
Phantosmias and phosphenes are common during RT. The treatment settings and individual arousal level influence the occurrence, intensity and hedonic of such abnormal sensations. Phantosmias and phosphenes may involve more central neural than peripheral mechanism, and they could be elicited with activation of areas that are not regarded to be part of the olfactory or visual network.
Topics: Humans; Female; Smell; Prospective Studies; Olfaction Disorders; Phosphenes; Emotions
PubMed: 37270715
DOI: 10.1007/s00066-023-02095-5 -
Behavioral and Brain Functions : BBF Dec 2023Parosmia is a qualitative olfactory dysfunction presenting as "distorted odor perception" in presence of an odor source. Aim of this study was to use resting state...
OBJECTIVE
Parosmia is a qualitative olfactory dysfunction presenting as "distorted odor perception" in presence of an odor source. Aim of this study was to use resting state functional connectivity to gain more information on the alteration of olfactory processing at the level of the central nervous system level.
METHODS
A cross sectional study was performed in 145 patients with parosmia (age range 20-76 years; 90 women). Presence and degree of parosmia was diagnosed on the basis of standardized questionnaires. Participants also received olfactory testing using the "Sniffin' Sticks". Then they underwent resting state scans using a 3 T magnetic resonance imaging scanner while fixating on a cross.
RESULTS
Whole brain analyses revealed reduced functional connectivity in salience as well as executive control networks. Region of interest-based analyses also supported reduced functional connectivity measures between primary and secondary olfactory eloquent areas (temporal pole, supramarginal gyrus and right orbitofrontal cortex; dorso-lateral pre-frontal cortex and the right piriform cortex).
CONCLUSIONS
Participants with parosmia exhibited a reduced information flow between memory, decision making centers, and primary and secondary olfactory areas.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Aged; Cross-Sectional Studies; Olfaction Disorders; Smell; Brain; Magnetic Resonance Imaging
PubMed: 38115149
DOI: 10.1186/s12993-023-00225-8