Odor Discrimination Research Articles

Calretinin-expressing neurons in the basal forebrain specifically contact granule cells in the olfactory bulb and modulate odor learning.

GABAergic neurons in basal forebrain (BF) nuclei project densely to all layers of the mouse main olfactory bulb (OB), the first relay in odor information processing. However, BF projection neurons are diverse and the contribution of each subtype to odor information processing is not known. In the present study, we used retrograde and anterograde tracing methods together with whole-brain light-sheet analyses, patch-clamp recordings coupled with optogenetic and chemogenetic approaches during spontaneous odor discrimination, and go/no-go odor discrimination/learning tests to characterize the synaptic targets in the OB of BF calretinin-expressing (CR+) GABAergic cells and to reveal their functional implications. We used mice of either sex to show that OB-projecting CR+ neurons innervate the bulbar granule cell layer but not the glomerular layer. Optogenetic stimulation of CR+ axonal projections in OB slices elicited monosynaptic GABAergic currents in granule cells (GCs). Retrograde rabies virus-based transsynaptic tracing experiments confirmed these synaptic connections and further suggested that CR+ neurons provide the principal, if not the unique, BF input onto GCs. Chemogenetic inhibition of CR+ neurons in the BF of male mice did not affect odor discrimination in habituation/dishabituation tasks but led to impairment in odor learning during go/no-go odor-associative tasks. Our results revealed a subtype-specific projection pattern in the OB of a select population of BF neurons and suggested that distinct BF GABAergic projections have distinct effects on odor information processing and learning.Significance statement The basal forebrain projects densely into the olfactory bulb and plays an important role in odor processing. The basal forebrain contains neurochemically distinct cellular populations but the contribution of each subtype to odor information processing is not known. We identified predominant, if not unique, synaptic connections between neurons in the basal forebrain that are characterized by the expression of calretinin (CR) and granule cells in the olfactory bulb. The detailed morpho-functional characterization of these connections based on anterograde, retrograde, and rabies-based transsynaptic labeling, patch-clamp recordings, optogenetics, and behavioral analyses indicated that these connections are GABAergic in nature and suggested that CR-expressing neurons in the basal forebrain are involved in odor learning.

Accumbal acetylcholine signals associative salience.

Learning in dynamic environments requires animals to not only associate cues with outcomes but also to determine cue salience, which modulates how quickly related associations are updated. While dopamine (DA) in the nucleus accumbens core (NAcc) has been implicated in learning associations, the mechanisms of salience are less understood. Here, we tested the hypothesis that acetylcholine (ACh) in the NAcc encodes cue salience. We conducted four odor discrimination experiments in rats while simultaneously measuring accumbal ACh and DA. We found that ACh developed characteristic dips to cues over learning before DA signals differentiated cues by value, with these dips persisting through value decreases and developing faster during meta-learning. The dips reflected the cue salience across learning stages and tasks, as predicted by a hybrid attentional associative learning model that integrated principles from the Mackintosh and Pearce-Hall models, suggesting that accumbal ACh signals encode salience and potentially gate the learning process.

Effects of Age and Atomoxetine on Olfactory Perception and Learning and Underlying Plasticity Mechanisms in Rats.

The locus coeruleus (LC) plays a vital role in cognitive function through norepinephrine release. Impaired LC neuronal health and function is linked to cognitive decline during ageing and Alzheimer's disease. This study investigates age-related alterations in olfactory detection and discrimination learning, along with its reversal, in Long-Evans rats, and examines the effects of atomoxetine (ATM), a norepinephrine uptake inhibitor, on these processes. Adult (6-9 months) and aged (22-24 months) Long-Evans rats underwent odour detection threshold experiments with saline and two doses of ATM (0.3 and 1 mg/kg). Reward-based odour discrimination learning included simple, difficult and reversal learning tasks. LC neuron density, dopamine beta-hydroxylase and norepinephrine transporter expression in the piriform cortex (PC) and orbitofrontal cortex were measured. Reversal learning and olfactory threat extinction were used to measure behavioural flexibility. Immunohistochemistry and western blotting were used to analyse phosphorylated cAMP response element binding protein (pCREB) and cFos expression and exvivo electrophysiology assessed long-term depression (LTD) in the PC. Whereas adult and aged cohorts showed similar odour detection and discrimination learning, fewer aged rats acquired reversal learning successfully. ATM improved reward-based odour discrimination in adults but hindered learning reversal. A delayed CREB phosphorylation in the posterior PC associated with atomoxetine administration possibly underlies learning enhancement. ATM resulted in less freezing behaviour in a threat conditioning and extinction paradigm at moderate, but not at higher doses. ATM administration exvivo prevented PC LTD. These findings highlight the intricate effects of atomoxetine, influenced by target structures, and suggest potential interactions with other neurotransmitters. Our results contribute to understanding the impact of ageing and norepinephrine enhancers on cognitive processes.

The AWC OFF neuron is important for attraction to 1-butanol in Caenorhabditis elegans.

C. elegans uses chemosensation to recognize a variety of odors, many of which are released by bacteria, the major food source of C. elegans . Specific amphid sensory neurons are known to detect different odorants. Here we show that the AWC OFF neuron detects the attractive odorant 1-butanol. Because few odorants that are specifically recognized by the AWC OFF neuron have been identified, we hope that the identification of this additional odorant will facilitate studies of the role of the AWC OFF neuron in odor detection and discrimination.

Olfactory dysfunction in schizophrenia and other psychotic disorders: A comprehensive and updated meta-analysis.

Olfaction plays a key role in our daily life, influencing food enjoyment, threat detection, mood and social relationships. Numerous studies have provided evidence of abnormal olfactory function in schizophrenia and other psychotic disorders. This pre-registered meta-analysis was conducted to (a) provide an updated overview of olfactory function in schizophrenia-spectrum disorders, and (b) examine the modulatory effects of demographic and clinical variables on distinct olfactory abilities. We complied with the PRISMA guidelines, searching throughout PubMed, MEDLINE, and PsycInfo, until the 12th of August 2023. A total of 73 publications were included, comprising data from 3282 patients and 3321 healthy controls. Results revealed that (a) patients performed significantly worse in higher-order olfactory tests (identification and discrimination) compared to healthy controls, while no differences were observed in odor sensitivity; (b) patients' performance in odor identification was moderated by education, as well as disease duration and negative symptoms. Our findings support the presence of olfactory impairments in schizophrenia-spectrum disorders, leading to significantly poorer performance in both odor identification and discrimination, but not sensitivity, when compared to healthy controls.

Six-week engagement in after-school activities involving chemosensory education does not affect olfactory abilities and personal significance of olfaction in 9-11-year-olds: Preliminary evidence.

Chemosensory learning is a lifelong process of acquiring perceptual expertise and semantic knowledge about chemical stimuli within the everyday environment. In the research context, it is usually simulated using olfactory training, which typically involves repeated exposure to a set of odors over a period of time. Following olfactory training, enhanced olfactory performance has been observed in adults, and similar evidence is beginning to emerge in children. However, the literature is scant concerning the effects of interventions that more closely resemble how chemosensory experience is acquired in daily life. Since children's chemosensory ecology appears to play a crucial role in olfactory development, we investigated whether engaging in activities that stimulate the chemical senses enhances olfactory performance and metacognition. To this end, we invited 20 children aged 9-11 years to participate in teacher-assisted after-school activities for 30-60 minutes a day for six weeks. During the odd weeks, the children appraised herbal and spice blends and used them to prepare dishes and make beauty products. During the even ones, they explored the city by smellwalking and created smellscape maps. The educational outcomes were evaluated using the Sniffin' Sticks test for odor identification and discrimination and the Children's Personal Significance of Olfaction. Bayesian analyses did not reveal any compelling evidence in support of the alternative hypothesis that children in the chemosensory education group outperform those in the comparison group at the post-test. Rates of reliable increase but also decrease in performance on the Sniffin' Sticks identification and discrimination tests were similar in both groups. We corroborated the previous findings regarding girls' and older children's greater proficiency at identifying odors and the female keener interest in the sense of smell. We offer several practical suggestions researchers may want to consider to tailor their research protocols to reflect more closely the broader context in which chemosensory learning takes place and better capture the nuanced outcomes of such interventions.

The activation of the piriform cortex to lateral septum pathway during chronic social defeat stress is crucial for the induction of behavioral disturbance in mice.

Chronic stress induces neural dysfunctions and risks mental illnesses. Clinical and preclinical studies have established the roles of brain regions underlying emotional and cognitive functions in stress and depression. However, neural pathways to perceive sensory stimuli as stress to cause behavioral disturbance remain unknown. Using whole-brain imaging of Arc-dVenus neuronal response reporter mice and machine learning analysis, here we unbiasedly demonstrated different patterns of contribution of widely distributed brain regions to neural responses to acute and chronic social defeat stress (SDS). Among these brain regions, multiple sensory cortices, especially the piriform (olfactory) cortex, primarily contributed to classifying neural responses to chronic SDS. Indeed, SDS-induced activation of the piriform cortex was augmented with repetition of SDS, accompanied by impaired odor discrimination. Axonal tracing and chemogenetic manipulation showed that excitatory neurons in the piriform cortex directly project to the lateral septum and activate it in response to chronic SDS, thereby inducing behavioral disturbance. These results pave the way for identifying a spatially defined sequence of neural consequences of stress and the roles of sensory pathways in perceiving chronic stress in mental illness pathology.

Ligand discrimination in hOR1A1 based on the capacitive response

Odorant discrimination mechanisms are based on the differential interactions between odorant molecules and olfactory receptors (ORs). Biohybrid sensors based on ORs described to date show selectivity towards specific versus non-specific binding of odorants, being unable to distinguish between specific ligands of different affinity. Here we disclose a method that enables odorant discrimination based on the modulation of the capacitive response of the receptor, which allows the differentiation of three high-affinity hOR1A1 agonists. We performed voltammetry and impedance measurements of the hOR1A1 receptor selectively immobilized on a gold electrode in the absence and presence of the agonists. Binding induces a decrease in the capacitive response of the receptor that is proportional to the ligand potency, reaching up to a 40% decrease for the cognate ligand dihydrojasmone, which is attributed to changes in the magnitude and orientation of the electric dipole in the receptor, thereby regulating its response to the applied electric field.

The neural substrate linking olfactory deficits to cognitive decline in MCI

AbstractBackgroundA combination of impairments in odor threshold and discrimination, which are both predominantly sensory level functions, and olfactory cognition contribute to age‐related odor‐identification deficits. However, in Alzheimer’s disease (AD), odor identification is more impaired compared to sensory‐level olfactory functions. We, therefore, hypothesized that match and mismatch olfactory fMRI tasks could be used to isolate areas of odor‐identification and that these areas would include primary as well as secondary olfactory structures. We combined functional magnetic resonance imaging (fMRI) with an olfactory detection task to investigate the neural substrates underlying odor identification.MethodTwenty‐five healthy controls and eighteen MCI subjects (Table 1) took part in an olfactory fMRI odor detection task. The task required subjects to press a button with their right index finger to identify an odorant (i.e., oddball) from a list of distractors. An out of magnet olfactory identification and threshold test was also conducted. This multiple‐choice test was used to measure a participants’ ability to identify twenty different odors.ResultA contrast of HC>MCI, for all odor conditions, yielded activation in brain regions shown in Figure 1C. These regions were used in a subsequent correlation analysis. The left supramarginal gyrus was included based on a study where the TPJ area (which includes parts of the supramarginal and superior temporal gyrus) was highly active in the left hemisphere. A correlation analyses using both HC and MCI showed significant positive correlations between activity in the L supramarginal, L superior temporal, L TPJ and L inferior frontal orbital areas, and out‐of‐magnet olfactory identification scores (Figure 2).ConclusionOur novel fMRI task elicited robust activation in higher‐order olfactory structures. Since Lower activation in these regions correlated with lower ID scores across the entire cohort. HC shows greater activity in higher order brain regions, suggesting an impaired top‐down identification mechanism in MCI. There seems to be a separation between HC and MCI in Figure 2. This will be further investigated using a larger sample size.

Characteristics of subjective olfactory dysfunction and imaging features in patients with traumatic olfactory disorders: a retrospective case-control study.

Olfactory dysfunction caused by head trauma poses significant challenges in clinical diagnosis and treatment. The primary difficulty arises from direct injuries to olfactory-related brain tissues. Although imaging provides the most direct method to evaluate such injuries, there is no standardized international diagnostic criterion for olfactory dysfunction based on imaging. We designed this study to compare the subjective olfactory function differences and brain gray-matter (GM) and white-matter (WM) volume differences between patients with traumatic olfactory dysfunction and those with other types of olfactory dysfunction and to determine the characteristics of subjective olfactory dysfunction and imaging features in patients with traumatic olfactory disorders. The findings of this study can provide a theoretical basis for the diagnosis of traumatic olfactory disorders. This ethics committee-approved, retrospective case-control study included 56 patients with traumatic olfactory dysfunction (trauma group) and 45 patients with other types of olfactory dysfunction (e.g., postinfection, nasal inflammation, idiopathic disease). The "Sniffin' Sticks" olfactory function test was used to analyze the subjective olfactory function differences between the two groups, and voxel-based morphometry (VBM) was used to compare the GM volume (GMV) and WM volume (WMV) of brain regions between the two groups. (I) There was no statistical difference in age distribution between the trauma group (41.55±11.77 years) and the control group (38.87±14.37 years; P>0.05). (II) The trauma group had significantly lower total scores and subtest scores on the Sniffin' Sticks olfactory test compared to the control group [odor threshold test (OT): 1.04±0.33 vs. 1.67±1.42; odor discrimination test (OD): 2.93±2.25 vs. 5.42±3.66; odor identification test (OI): 2.77±1.94 vs. 6.71±3.55; total scores: 6.74±3.91 vs. 13.81±7.63; all P values <0.05]. (III) Compared with the control group, the trauma group had significantly reduced GMV and WMV in the bilateral orbitofrontal cortex, bilateral anterior cingulate gyrus, bilateral cingulate gyrus, bilateral rectus gyrus, bilateral olfactory cortex, right superior frontal gyrus, bilateral insula, bilateral caudate nucleus, and bilateral thalamus [Pfamily-wise error (FWE)<0.05]. (IV) There was a significant positive correlation between the odor identification function scores and GMV in certain brain regions (PFWE<0.05), and the GMV in these regions was reduced in the trauma group compared to the control group. Compared to patients with other types of olfactory dysfunction, patients with traumatic olfactory dysfunction have poorer subjective olfactory functions and more severe damage to olfactory-related brain regions, including the bilateral orbitofrontal cortex, anterior cingulate gyrus, cingulate gyrus, rectus gyrus, insula, and olfactory cortex. The olfactory nerve damage in these brain regions can be used as a basis for the diagnosis of traumatic olfactory disorders.

A novel 14mer peptide, T14, is associated with age-dependent behaviour in female mice.

Age-related cognitive decline presents a healthcare challenge. While age-related mechanisms are mainly studied in humans, animal models provide key insights. Despite evidence of sex-specific differences in aging and cognition, the impact of age on female rodent behaviour is underexplored. This study investigated age-related behavioural changes in female C57BL/6 mice over 8 months, alongside neurochemical markers amyloid, Tau, and T14, a novel peptide from acetylcholinesterase (AChE) that promotes cell growth/renewal. Behavioural assessments showed an age-dependent decline in nest-building ability and familiar odour discrimination from 10 months. Spatial learning declined at 10 and 13 months, while object recognition memory remained intact from 5 to 13 months of age. Neurochemical analyses revealed a decline in T14 and its receptor α7-AChR during postnatal development and adulthood. However, there was a disparity between AChE expression and its enzymatic activity. T14 levels correlated with phosphorylated tau, but not amyloid, and negatively with nest-building scores, suggesting a role of T14 in age-related behavioural changes. This study highlights early behavioural and molecular indicators of cognitive decline in middle-aged female mice.

Representational learning by optimization of neural manifolds in an olfactory memory network.

Higher brain functions depend on experience-dependent representations of relevant information that may be organized by attractor dynamics or by geometrical modifications of continuous "neural manifolds". To explore these scenarios we analyzed odor-evoked activity in telencephalic area pDp of juvenile and adult zebrafish, the homolog of piriform cortex. No obvious signatures of attractor dynamics were detected. Rather, olfactory discrimination training selectively enhanced the separation of neural manifolds representing task-relevant odors from other representations, consistent with predictions of autoassociative network models endowed with precise synaptic balance. Analytical approaches using the framework of manifold capacity revealed multiple geometrical modifications of representational manifolds that supported the classification of task-relevant sensory information. Manifold capacity predicted odor discrimination across individuals, indicating a close link between manifold geometry and behavior. Hence, pDp and possibly related recurrent networks store information in the geometry of representational manifolds, resulting in joint sensory and semantic maps that may support distributed learning processes.

Engineered odorant receptors illuminate the basis of odour discrimination.

How the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations remains poorly understood. Vertebrate animals perceive odours through G protein-coupled odorant receptors (ORs)1. In humans, around 400 ORs enable the sense of smell. The OR family comprises two main classes: class I ORs are tuned to carboxylic acids whereas class II ORs, which represent most of the human repertoire, respond to a wide variety of odorants2. A fundamental challenge in understanding olfaction is the inability to visualize odorant binding to ORs. Here we uncover molecular properties of odorant-OR interactions by using engineered ORs crafted using a consensus protein design strategy3. Because such consensus ORs (consORs) are derived from the 17 major subfamilies of human ORs, they provide a template for modelling individual native ORs with high sequence and structural homology. The biochemical tractability of consORs enabled the determination of four cryogenic electron microscopy structures of distinct consORs with specific ligand recognition properties. The structure of a class I consOR, consOR51, showed high structural similarity to the native human receptor OR51E2 and generated a homology model of a related member of the human OR51 family with high predictive power. Structures of three class II consORs revealed distinct modes of odorant-binding and activation mechanisms between class I and class II ORs. Thus, the structures of consORs lay the groundwork for understanding molecular recognition of odorants by the OR superfamily.

The Infralimbic, but not the Prelimbic Cortex is needed for a Complex Olfactory Memory Task.

The medial prefrontal cortex (mPFC) plays a key role in memory and behavioral flexibility, and a growing body of evidence suggests that the prelimbic (PL) and infralimbic (IL) subregions contribute differently to these processes. Studies of fear conditioning and goal-directed learning suggest that the PL promotes behavioral responses and memory retrieval, while the IL inhibits them. Other studies have shown that the mPFC is engaged under conditions of high interference. This raises the possibility that the PL and IL play differing roles in resolving interference. To examine this, we first used chemogenetics (DREADDs) to suppress mPFC neuronal activity and tested subjects on a conditional discrimination task known to be sensitive to muscimol inactivation. After confirming the effectiveness of the DREADD procedures, we conducted a second experiment to examine the PL and IL roles in a high interference memory task. We trained rats on two consecutive sets of conflicting odor discrimination problems, A and B, followed by test sessions involving a mid-session switch between the problem sets. Controls repeatedly performed worse on Set A, suggesting that learning Set B inhibited the rats' ability to retrieve Set A memories (i.e. retroactive interference). PL inactivation rats performed similarly to controls. However, IL inactivation rats did not show this effect, suggesting that the IL plays a critical role in suppressing the retrieval of previously acquired memories that may interfere with retrieval of more recent memories. These results suggest that the IL plays a critical role in memory control processes needed for resolving interference.

Clinical efficacy of olfactory training using aromatic traditional Chinese medicine in managing olfactory dysfunction induced by SARS-CoV-2.

The aim of this study is to assess the clinical efficacy of olfactory training using aromatic traditional Chinese medicine (TCM) for addressing severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced olfactory dysfunction, while also exploring the factors that influence the observed efficacy. 172 outpatients with SARS-CoV-2-related olfactory dysfunction were randomized into two groups. The experimental group received olfactory training with TCM aromatics (ginger, Pericarpium Citri Reticulatae, Santali Albi Lignum, Styrax), while the control group used non-TCM aromatics (phenyl ethanol-rose, menthol-mint, citronellal-lemon, eugenol-clove) for 24 weeks. Olfactory function was assessed using the Sniffin' Sticks test and TDI (threshold-discrimination-identification) scores at baseline, 1, 3, and 6 months post-treatment. Response rates at 1, 3, and 6 months post-treatment were 3.66%, 25.61%, and 43.90% in the experimental group, and 4.94%, 23.46%, and 43.21% in the control group. The TDI scores of the experimental group and the control group were statistically different before and after treatment. At 3 and 6 months post-treatment, TDI scores increased significantly, with enhanced odor discrimination and identification capabilities in both groups compared to pre-treatment, while the odor detection threshold was not improved compared with that before treatment. At the 3- and 6-month follow-ups, experimental group showed significantly higher self-rated sleep and anxiety scores than controls, indicating notable improvement in both after treatment. Olfactory training with aromatic TCM offers an effective treatment for SARS-CoV-2-induced olfactory dysfunction, improving odor discrimination, identification without significant differences compared to conventional aromatics, besides, it may also improve anxiety and sleep quality.

Normative data for the lateralization task in the assessment of intranasal trigeminal function.

To provide normative data for the lateralization task in the assessment of intranasal trigeminal function, as well as to investigate potential effects of age, sex and olfactory function. The lateralization task using eucalyptus as target stimulus was performed to assess intranasal trigeminal function. Data were collected from: 360 healthy adult participants (mean age 37.5 ± 17.4) for the 40-trial version; 284 participants (mean age 32.6 ± 4.1) for the 20-trial version; and 418 participants (mean age 42.6 ± 15.6) for the 10-trial version. The "Sniffin Sticks" test was used to measure olfactory function. The mean scores were 35.46 ± 4.50 for the 40-trial version, 15.64 ± 3.65 for the 20-trial version, and 8.14 ± 2.16 for the 10-trial version. In the reference group aged 18-25 years, the 10th percentiles were 33 for the 40-trial version, 11 for the 20-trial version, and 6 for the 10-trial version. Significant effects of age and odor discrimination score were observed on lateralization performance. We provide reference scores for the lateralization task, in large sample of healthy participants. Among the three examined tasks (40, 20 and 10), the 40-trial task yielded the most reliable information. For the 40-trial version, scores equal or higher to 33 points indicate a normal lateralization ability, whereas scores between 27 and 32 may warrant further assessment. Scores below 27 possibly point towards a decreased trigeminal function. The lateralization task serves as surrogate marker of intranasal trigeminal functions and further studies with pathological cases are needed to explore its clinical usefulness.

Structural Basis for Histaminergic Regulation of Neural Circuits in the Mouse Olfactory Bulb.

Odor information is modulated by centrifugal inputs from other brain regions to the olfactory bulb (OB). Neurons containing monoamines, such as serotonin, acetylcholine, and noradrenaline, are well known as centrifugal inputs; however, the role of histamine, which is also present in the OB, is not well understood. In this study, we examined the histaminergic neurons projecting from the hypothalamus to the OB. We used an antibody against histidine decarboxylase (HDC), a synthesizing enzyme of histamine, to identify histaminergic neurons and assess their localization within the OB and the ultrastructure of their fibers and synapses using multiple immunostaining laser microscopy, ultra-high voltage electron microscopy (EM), and EM to confirm their relationships with other neurons. To further identify the origin nucleus of the histaminergic neurons projecting to the OB, we injected the retrograde tracer FluoroGold and analyzed the pathway to the OB anterogradely. HDC-immunoreactive (-ir) fibers were abundant in the olfactory nerve (ON) layer compared to other monoamines. HDC-ir neurons received asymmetrical synapses from ONs and formed synapses containing pleomorphic vesicles with variable postsynaptic densities to non-ON elements, thus forming serial synapses. We also confirmed that histaminergic neurons project from the rostral ventral tuberomammillary nucleus to the granule cell layer of the OB and, for the first time, successfully visualized their axons from the hypothalamus to the OB. These findings indicate that histamine may regulate odor discrimination in the OB, suggesting a regulatory relationship between hypothalamic function and olfaction. We thus elucidate morphological mechanisms with tuberomammillary nucleus-derived histaminergic neurons involved in olfactory information.

Neuroimaging evaluations of olfactory, gustatory, and neurological deficits in patients with long-term sequelae of COVID-19

The World Health Organization indicated that around 36 million of patients in the European Region showed long COVID associated with olfactory and gustatory deficits. The precise mechanism underlying long COVID clinical manifestations is still debated. The aim of this study was to evaluate potential correlations between odor threshold, odor discrimination, odor identification, and the activation of specific brain areas in patients after COVID-19. Sixty subjects, 27 patients (15 women and 12 men) with long COVID and a mean age of 40.6 ± 13.4 years, were compared to 33 age-matched healthy controls (20 women and 13 men) with a mean age of 40.5 ± 9.8 years. Our data showed that patients with long COVID symptoms exhibited a significant decrease in odor threshold, odor discrimination, odor identification, and their sum TDI score compared to age-matched healthy controls. In addition, our results indicated significant correlations between odor discrimination and the increased activation in the right hemisphere, in the frontal pole, and in the superior frontal gyrus. This study indicated that the resting-state fMRI in combination with the objective evaluation of olfactory and gustatory function may be useful for the evaluation of patients with long COVID associated with anosmia and hyposmia.

Studying the Effects of Inhaled Environmental Pollutants on Olfactory Function in Mice.

Olfactory impairment is a significant public health problem and independently predicts the risk of neurodegenerative diseases. Inhaled environmental pollutants exposure may impair olfaction; thereby, there is an urgent need for methods to evaluate the effects of inhaled environmental pollutants exposure on olfaction. Mice are ideal models for olfactory experiments because of their highly developed olfactory system and behavioral characteristics. To assess the effects of inhaled environmental pollutants exposure on olfactory function in mice, a detailed buried food test and social odor discrimination experiment is provided, including the experiment preparation, the selection and construction of experimental facilities, the testing process, and indexes of time. Meanwhile, timekeeping equipment, operational details, and the experimental environment are discussed to ensure the success of the assay. Zinc sulfate is used as the treatment to demonstrate the feasibility of the experimental approach. The protocol provides a simple and clear operational process for assessing the effects of inhaled environmental pollutants on olfactory function in mice.

Four odorants for olfactory training are enough: a pilot study

Background: Olfactory training (OT) is commonly used for the treatment of olfactory disorders. Nevertheless, there is an ongoing debate about the most effective OT regimen. We aimed to compare the effects of OT with 7 items (rose, lemon, eucalyptus, cloves, stewed apple, balm, mint) to 4-item-OT (rose, lemon, eucalyptus, cloves) over 3 months. Methods: Participants were 40 patients with olfactory dysfunction receiving 4-item-OT or 7-item-OT and 60 gender- and age-matched individuals with normal sense of smell receiving no OT, 4-item-OT, or 7-item-OT. Before and after the OT we assessed n-butanol odor thresholds, discrimination, and identification (TDI score), additionalthresholds for (R)-(-)-carvone, β-damascenone, salicyclic acid benzylester, the degree of phantosmia and parosmia, cognitive function, and ratings of olfactory function. Results: In both patient groups, the TDI score increased with the use of OT, regardless of the number of odors used (p < 0.001; 3.48 ± 4.21 and lower than control groups). The clinically significant increase of 5.5 points in TDI score correlated with change of ratings of parosmia (r 0.62; p < 0.01) and with ratings of olfactory dysfunction (r = 0.51; p < 0.05). Conclusion: Concluding, OT over a 3-months period with 4 or 7 odors appears to produce similar results, although the sample size has to be considered.