Smell and taste in idiopathic blepharospasm

The pathophysiology of blepharospasm is incompletely understood. Current concepts suggest that blepharospasm is a network disorder, involving basal ganglia, thalamus, cortex, and, possibly, the cerebellum. Tracing, imaging, and clinical studies revealed that these structures are also concerned with olfaction and taste. Because of this anatomical overlap, dysfunction of the chemical senses in blepharospasm is expected. Injections of botulinum toxin into the eyelid muscles are the first-line treatment of blepharospasm. Yet, the effects of botulinum toxin on the chemical senses have not been systematically assessed. To contribute to a better understanding of blepharospasm, olfactory and gustatory abilities were assessed in 17 subjects with blepharospasm and 17 age-/sex-matched healthy controls. Sniffin Sticks were used to assess odor threshold, odor discrimination, and odor identification. Results of these three Sniffin Sticks subtests were added to the composite olfactory score. The Taste Strips were applied to assess taste. In an adjacent study, we assessed the sense of smell and taste in eight subjects with blepharospasm before and 4 weeks after botulinum toxin treatment. Subjects with blepharospasm had significantly lower (= worse) scores for odor threshold and for the composite olfactory score than healthy controls, while odor discrimination, odor identification, and the composite taste score were not different between groups. The adjacent study revealed that botulinum toxin did not impact the chemical senses. In this study, subjects with blepharospasm had a lower (= worse) odor threshold than healthy controls. As olfaction is important in daily life, findings justify further research of olfaction in blepharospasm.

Multi-Odor Discrimination by Rat Sniffing for Potential Monitoring of Lung Cancer and Diabetes

The discrimination learning of multiple odors, in which multi-odor can be associated with different responses, is important for responding quickly and accurately to changes in the external environment. However, very few studies have been done on multi-odor discrimination by animal sniffing. Herein, we report a novel multi-odor discrimination system by detection rats based on the combination of 2-Choice and Go/No-Go (GNG) tasks into a single paradigm, in which the Go response of GNG was replaced by 2-Choice, for detection of toluene and acetone, which are odor indicators of lung cancer and diabetes, respectively. Three of six trained rats reached performance criterion, in 12 consecutive successful tests within a given set or over 12 sets with a success rate of over 90%. Through a total of 1300 tests, the trained animals (N = 3) showed multi-odor sensing performance with 88% accuracy, 87% sensitivity and 90% specificity. In addition, a dependence of behavior response time on odor concentrations under given concentration conditions was observed, suggesting that the system could be used for quantitative measurements. Furthermore, the animals’ multi-odor sensing performance has lasted for 45 days, indicating long-term stability of the learned multi-odor discrimination. These findings demonstrate that multi-odor discrimination can be achieved by rat sniffing, potentially providing insight into the rapid, accurate and cost-effective multi-odor monitoring in the lung cancer and diabetes.

Olfactory Performance in Youth With Full and Subthreshold Avoidant/Restrictive Food Intake Disorder

Background: Avoidant/restrictive (A/R) food intake disorder (ARFID) is characterized by restrictive eating defined by lack of interest in food, sensory sensitivity, and/or fear of aversive consequences of eating resulting in a failure to meet adequate nutritional and/or energy needs. The complex psychopathology that differentiates ARFID from other eating disorders highlights the need to explore the role of sensory systems in disease etiology. Olfaction has an important role in eating behavior. Specifically, olfactory dysfunction is associated with decreased food intake and appetite. Olfactory performance and associated clinical characteristics have yet to be examined in individuals with ARFID. We hypothesized that higher levels of PYY, which signals satiety, would be associated with poorer olfactory performance; whereas greater food fussiness and A/R eating severity would be associated with stronger olfactory performance. Methods: We evaluated a cross-sectional sample of children and adolescents with full and subthreshold ARFID (n=82, 46.2% female, mean age 15.8±3.8). We measured olfactory performance with the Sniffin’ Sticks test (Burghardt®, Wedel, Germany) which captures odor discrimination, odor identification, and odor threshold. Higher scores on all three indices represent stronger olfactory performance. We also measured fasting serum PYY; severity of A/R eating on the Pica, ARFID and Rumination Disorder Interview (PARDI); and food fussiness as a measure of food-related sensory sensitivity on the Adult Eating Behavior Questionnaire. Statistical analyses included T-test and spearman’s correlations. Results: Greater fasting serum PYY levels were associated with significantly poorer performance on the odor threshold test (r=-0.4, p=0.003). Greater severity of A/R eating (r=-0.3 p=0.008) and food fussiness (r=-0.2, p=0.03) were both associated with significantly poorer performance on the odor discrimination test. Conclusions: As predicted, we found that higher levels of PYY were associated with poorer olfactory performance in youth with full and subthreshold ARFID. However, contrary to hypotheses, we found that greater food fussiness and severity of A/R eating were associated with poorer olfactory performance. Future research should investigate whether high levels of PYY and poor olfactory performance are causes, consequences, or correlates of A/R eating.

The Role of Knockout Olfactory Receptor Genes in Odor Discrimination

To date, little is known about the role of olfactory receptor (OR) genes on smell performance. Thanks to the availability of whole-genome sequencing data of 802 samples, we identified 41 knockout (KO) OR genes (i.e., carriers of Loss of Function variants) and evaluated their effect on odor discrimination in 218 Italian individuals through recursive partitioning analysis. Furthermore, we checked the expression of these genes in human and mouse tissues using publicly available data and the presence of organ-related diseases in human KO (HKO) individuals for OR expressed in non-olfactory tissues (Fisher test). The recursive partitioning analysis showed that age and the high number (burden) of OR-KO genes impact the worsening of odor discrimination (p-value < 0.05). Human expression data showed that 33/41 OR genes are expressed in the olfactory system (OS) and 27 in other tissues. Sixty putative mouse homologs of the 41 humans ORs have been identified, 58 of which are expressed in the OS and 37 in other tissues. No association between OR-KO individuals and pathologies has been detected. In conclusion, our work highlights the role of the burden of OR-KO genes in worse odor discrimination.

Olfactory Detection of Toluene by Detection Rats for Potential Screening of Lung Cancer

Early detection is critical to successfully eradicating a variety of cancers, so the development of a new cancer primary screening system is essential. Herein, we report an animal nose sensor system for the potential primary screening of lung cancer. To establish this, we developed an odor discrimination training device based on operant conditioning paradigms for detection of toluene, an odor indicator component of lung cancer. The rats (N = 15) were trained to jump onto a floating ledge in response to toluene-spiked breath samples. Twelve rats among 15 trained rats reached performance criterion in 12 consecutive successful tests within a given set, or over 12 sets, with a success rate of over 90%. Through a total of 1934 tests, the trained rats (N = 3) showed excellent performance for toluene detection with 82% accuracy, 83% sensitivity, 81% specificity, 80% positive predictive value (PPV) and 83% negative predictive value (NPV). The animals also acquired considerable performance for odor discrimination even in rigorous tests, validating odor specificity. Since environmental and long-term stability are important factors that can influence the sensing results, the performance of the trained rats was studied under specified temperature (20, 25, and 30 °C) and humidity (30%, 45%, and 60% RH) conditions, and monitored over a period of 45 days. At given conditions of temperature and humidity, the animal sensors showed an average accuracy within a deviation range of ±10%, indicating the excellent environmental stability of the detection rats. Surprisingly, the trained rats did not differ in retention of last odor discrimination when tested 45 days after training, denoting that the rats’ memory for trained odor is still available over a long period of time. When taken together, these results indicate that our odor discrimination training system can be useful for non-invasive breath testing and potential primary screening of lung cancer.

Locus Coeruleus Activation Patterns Differentially Modulate Odor Discrimination Learning and Odor Valence in Rats

The locus coeruleus (LC) produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence encoding of sensory information are unknown. Here we show bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 msec or 10 sec accelerated acquisition of a similar odor discrimination. Similar odor discrimination learning was impaired by noradrenergic blockade in the piriform cortex (PC). However, 10-Hz phasic light-mediated learning facilitation was prevented by a dopaminergic antagonist in the PC, or by ventral tegmental area (VTA) silencing with lidocaine, suggesting a LC-VTA-PC dopamine circuitry involvement. Ten hertz tonic stimulation did not alter odor discrimination acquisition, and was ineffective in activating VTA DA neurons. For valence encoding, tonic stimulation at 25 Hz induced conditioned odor aversion, while 10-Hz phasic stimulations produced an odor preference. Both conditionings were prevented by noradrenergic blockade in the basolateral amygdala (BLA). Cholera Toxin B retro-labeling showed larger engagement of nucleus accumbens-projecting neurons in the BLA with 10-Hz phasic activation, and larger engagement of central amygdala projecting cells with 25-Hz tonic light. These outcomes argue that the LC activation patterns differentially influence both target networks and behavior.