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.

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.

Long-Term Taste and Smell Outcomes After COVID-19.

Importance: Self-report surveys suggest that long-lasting taste deficits may occur after SARS-CoV-2 infection, influencing nutrition, safety, and quality of life. However, self-reports of taste dysfunction are inaccurate, commonly reflecting deficits due to olfactory not taste system pathology; hence, quantitative testing is needed to verify the association of post-COVID-19 condition with taste function. Objective: To use well-validated self-administered psychophysical tests to investigate the association of COVID-19 with long-term outcomes in taste and smell function. Design, Setting, and Participants: This nationwide cross-sectional study included individuals with and without a prior history of COVID-19 recruited from February 2020 to August 2023 from a social media website (Reddit) and bulletin board advertisements. In the COVID-19 cohort, there was a mean of 395 days (95% CI, 363-425 days) between diagnosis and testing. Exposure: History of COVID-19. Main Outcomes and Measures: The 53-item Waterless Empirical Taste Test (WETT) and 40-item University of Pennsylvania Smell Identification Test (UPSIT) were used to assess taste and smell function. Total WETT and UPSIT scores and WETT subtest scores of sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate were assessed for groups with and without a COVID-19 history. The association of COVID-19 with taste and smell outcomes was assessed using analysis of covariance, χ2, and Fisher exact probability tests. Results: Tests were completed by 340 individuals with prior COVID-19 (128 males [37.6%] and 212 females [62.4%]; mean [SD] age, 39.04 [14.35] years) and 434 individuals with no such history (154 males [35.5%] and 280 females [64.5%]; mean (SD) age, 39.99 [15.61] years). Taste scores did not differ between individuals with and without previous COVID-19 (total WETT age- and sex-adjusted mean score, 33.41 [95% CI, 32.37-34.45] vs 33.46 [95% CI, 32.54-34.38]; P = .94). In contrast, UPSIT scores were lower in the group with previous COVID-19 than the group without previous COVID-19 (mean score, 34.39 [95% CI, 33.86-34.92] vs 35.86 [95% CI, 35.39-36.33]; P < .001]); 103 individuals with prior COVID-19 (30.3%) and 91 individuals without prior COVID-19 (21.0%) had some degree of dysfunction (odds ratio, 1.64 [95% CI, 1.18-2.27]). The SARS-CoV-2 variant present at the time of infection was associated with smell outcomes; individuals with original untyped and Alpha variant infections exhibited more loss than those with other variant infections; for example, total to severe loss occurred in 10 of 42 individuals with Alpha variant infections (23.8%) and 7 of 52 individuals with original variant infections (13.5%) compared with 12 of 434 individuals with no COVID-19 history (2.8%) (P < .001 for all). Conclusions and Relevance: In this study, taste dysfunction as measured objectively was absent 1 year after exposure to COVID-19 while some smell loss remained in nearly one-third of individuals with this exposure, likely explaining taste complaints of many individuals with post-COVID-19 condition. Infection with earlier untyped and Alpha variants was associated with the greatest degree of smell loss.

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.

The neural representations of valence transformation in indole processing.

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.

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.

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.

Development of an automated human scent olfactometer and its use to evaluate detection dog perception of human scent.

Working Dogs have shown an extraordinary ability to utilize olfaction for victim recovery efforts. Although instrumental analysis has chemically characterized odor volatiles from various human biospecimens, it remains unclear what perceptually constitutes human scent (HS) for dogs. This may be in part due to the lack of methodology and equipment to train and evaluate HS perception. The aims of this research were 1) to develop an automated human scent olfactometer (AHSO) to present HS to dogs in a controlled setting and 2) use the AHSO to evaluate dogs' response to different scented articles and individual components of HS. A human volunteer was placed in a clear acrylic chamber and using a vacuum pump and computer-controlled valves, the headspace of this chamber was carried to one of three ports in a different room. Dogs were trained to search all three ports of the olfactometer and alert to the one containing HS. In Experiment 1 and 2, the AHSO was validated by testing two dogs naïve to HS (Experiment 1) and five certified Search and Rescue (SAR) teams naïve to the apparatus (Experiment 2). All dogs showed sensitivity and specificity to HS > 95% in the apparatus. In Experiment 3, we used a spontaneous generalization paradigm to evaluate generalization from the HS chamber to different scented articles exposed to the same volunteer and to a breath sample. Dogs' response rate to the different scented articles was < 10% but exceeded 40% for the breath sample. In Experiment 4, we replicated this result by re-testing spontaneous generalization to breath and when the volunteer had breath exhausted/removed from the chamber. Dogs' response rate to breath alone was 88% and only 50% when breath was removed. Altogether, the data indicate that exhaled breath is an important and salient component of HS under these conditions.

Molecular mechanisms of differentiation and class choice of olfactory sensory neurons.

The sense of smell is intricately linked to essential animal behaviors necessary for individual survival and species preservation. During vertebrate evolution, odorant receptors (ORs), responsible for detecting odor molecules, have evolved to adapt to changing environments, transitioning from aquatic to terrestrial habitats and accommodating increasing complex chemical environments. These evolutionary pressures have given rise to the largest gene family in vertebrate genomes. Vertebrate ORs are phylogenetically divided into two major classes; class I and class II. Class I OR genes, initially identified in fish and frog, have persisted across vertebrate species. On the other hand, class II OR genes are unique to terrestrial animals, accounting for ~90% of mammalian OR genes. In mice, each olfactory sensory neuron (OSN) expresses a single functional allele of a single OR gene from either the class I or class II OR repertoire. This one neuron-one receptor rule is established through two sequential steps: specification of OR class and subsequent exclusive OR expression from the corresponding OR class. Consequently, OSNs acquire diverse neuronal identities during the process of OSN differentiation, enabling animals to detect a wide array of odor molecules. This review provides an overview of the OSN differentiation process through which OSN diversity is achieved, primarily using the mouse as a model animal.

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.

Distinct subpopulations of ventral pallidal cholinergic projection neurons encode valence of olfactory stimuli.

To better understand the function of cholinergic projection neurons in the ventral pallidum (VP), we examined behavioral responses to appetitive (APP) and aversive (AV) odors that elicited approach or avoidance, respectively. Exposure to each odor increased cFos expression and calcium signaling in VP cholinergic neurons. Activity and Cre-dependent viral vectors selectively labeled VP cholinergic neurons that were activated and reactivated in response to either APP or AV odors, but not both, identifying two non-overlapping populations of VP cholinergic neurons differentially activated by the valence of olfactory stimuli. These two subpopulations showed differences in electrophysiological properties, morphology, and projections to the basolateral amygdala. Although VP neurons are engaged in both approach and avoidance behavioral responses, cholinergic signaling is only required for approach behavior. Thus, two distinct subpopulations of VP cholinergic neurons differentially encode valence of olfactory stimuli and play distinct roles in approach and avoidance behaviors.

A mechanosensory feedback that uncouples external and self-generated sensory responses in the olfactory cortex.

Sampling behaviors have sensory consequences that can hinder perceptual stability. In olfaction, sniffing affects early odor encoding, mimicking a sudden change in odor concentration. We examined how the inhalation speed affects the representation of odor concentration in the main olfactory cortex. Neurons combine the odor input with a global top-down signal preceding the sniff and a mechanosensory feedback generated by the air passage through the nose during inhalation. Still, the population representation of concentration is remarkably sniff invariant. This is because the mechanosensory and olfactory responses are uncorrelated within and across neurons. Thus, faster odor inhalation and an increase in concentration change the cortical activity pattern in distinct ways. This encoding strategy affords tolerance to potential concentration fluctuations caused by varying inhalation speeds. Since mechanosensory reafferences are widespread across sensory systems, the coding scheme described here may be a canonical strategy to mitigate the sensory ambiguities caused by movements.

One-trial odour recognition learning and its underlying brain areas in the zebrafish.

Distinguishing familiar from novel stimuli is critical in many animals' activities, and procedures based on this ability are among the most exploited in translational research in rodents. However, recognition learning and the underlying brain substrates remain unclear outside a few mammalian species. Here, we investigated one-trial recognition learning for olfactory stimuli in a teleost fish using a behavioural and molecular approach. With our behavioural analysis, we found that zebrafish can learn to recognise a novel odour after a single encounter and then, discriminate between this odour and a different one provided that the molecular structure of the cues is relatively differentiated. Subsequently, by expression analysis of immediate early genes in the main brain areas, we found that the telencephalon was activated when zebrafish encountered a familiar odour, whereas the hypothalamus and the optic tectum were activated in response to the novel odour. Overall, this study provided evidence of single-trial spontaneous learning of novel odours in a teleost fish and the presence of multiple neural substrates involved in the process. These findings are promising for the development of zebrafish models to investigate cognitive functions.

Olfactory information processing viewed through mitral and tufted cell-specific channels.

Parallel processing is a fundamental strategy of sensory coding. Through this processing, unique and distinct features of sensations are computed and projected to the central targets. This review proposes that mitral and tufted cells, which are the second-order projection neurons in the olfactory bulb, contribute to parallel processing within the olfactory system. Based on anatomical and functional evidence, I discuss potential features that could be conveyed through the unique channel formed by these neurons.

Behavioral discrimination and olfactory bulb encoding of odor plume intermittency.

In order to survive, animals often need to navigate a complex odor landscape where odors can exist in airborne plumes. Several odor plume properties change with distance from the odor source, providing potential navigational cues to searching animals. Here, we focus on odor intermittency, a temporal odor plume property that measures the fraction of time odor is above a threshold at a given point within the plume and decreases with increasing distance from the odor source. We sought to determine if mice can use changes in intermittency to locate an odor source. To do so, we trained mice on an intermittency discrimination task. We establish that mice can discriminate odor plume samples of low and high intermittency and that the neural responses in the olfactory bulb can account for task performance and support intermittency encoding. Modulation of sniffing, a behavioral parameter that is highly dynamic during odor-guided navigation, affects both behavioral outcome on the intermittency discrimination task and neural representation of intermittency. Together, this work demonstrates that intermittency is an odor plume property that can inform olfactory search and more broadly supports the notion that mammalian odor-based navigation can be guided by temporal odor plume properties.

Metabolic state modulates neural processing of odors in the human olfactory bulb.

The olfactory and endocrine systems have recently been shown to reciprocally shape the homeostatic processes of energy intake. As demonstrated in animal models, the individual's metabolic state dynamically modulates how the olfactory bulb process odor stimuli using a range of endocrine signals. Here we aimed to determine whether the neural processing of odors in human olfactory bulb is modulated by metabolic state. Participants were exposed to food-associated odors, in separate sessions being hungry and sated, while neural responses from the olfactory bulb was obtained using electrobulbogram. We found significantly higher gamma power activity (51-100 Hz) in the OB's response to odors during the Hunger compared to Sated condition. Specifically, EBG gamma power were elevated while hungry already at 100 ms after odor onset, thereby suggesting intra-bulbar modulation according to metabolic state. These results demonstrate that, akin to other animal models, hunger state affects OB activity in humans. Moreover, we show that the EBG method has the potential to measure internal metabolic states and, as such, could be used to study specificities in olfactory processing of individuals suffering from pathologies such as obesity or anorexia.

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.

Type 2 and Non-type 2 Inflammation in the Upper Airways: Cellular and Molecular Alterations in Olfactory Neuroepithelium Cell Populations.

PURPOSE OF REVIEW: Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this review, we describe the neurobiology of olfaction and the olfactory alterations in chronic rhinosinusitis with nasal polyps (type 2 inflammation) and post-viral acute rhinosinusitis (non-type 2 inflammation), highlighting the role of immune response attenuating olfactory neurogenesis as a possibly mechanism for the loss of smell in these diseases. RECENT FINDINGS: Several studies have provided relevant insights into the role of basal stem cells as direct participants in the progression of chronic inflammation identifying a functional switch away from a neuro-regenerative phenotype to one contributing to immune defense, a process that induces a deficient replacement of olfactory neurons. The interaction between olfactory stem cells and immune system might critically underlie ongoing loss of smell in type 2 and non-type 2 inflammatory upper airway diseases. In this review, we describe the neurobiology of olfaction and the olfactory alterations in type 2 and non-type 2 inflammatory upper airway diseases, highlighting the role of immune response attenuating olfactory neurogenesis, as a possibly mechanism for the lack of loss of smell recovery.

Taste and smell function in Wilson's disease.

OBJECTIVE: Wilson's disease (WD) is a metabolic disorder associated with abnormal copper metabolism that results in hepatic, psychiatric, and neurologic symptoms. No investigation of taste function has been made in patients with WD, although olfactory dysfunction has been evaluated. METHODS: Quantitative taste and smell test scores of 29 WD patients were compared to those of 790 healthy controls. Taste was measured using the 53-item Waterless Empirical Taste Test (WETT®) and smell using the 40-item revised University of Pennsylvania Smell Identification Test (R-UPSIT®). Multiple linear regression analysis controlled for age and sex. RESULTS: Average WETT® scores did not differ meaningfully between WD and control subjects (respective medians & IQRs = 32 [28-42] & 34 [27-41]); linear regression coefficient = 1.19, 95% CI [-0.81, 3.19], p = 0.242). In contrast, WD was associated with significantly reduced olfactory function [respective median (IQR) R-UPSIT® scores = 35 (33-37) vs. 37 (35-38); adjusted linear regression coefficient = -1.59, 95% CI [-2.34, -0.833]; p < 0.001)]. Neither olfaction nor taste were influenced by WD symptom subtype [23 (79.3%) were hepatic-predominant; 6 (20.7%) neurologic predominant]; R-UPSIT®, p = 0.774; WETT®, p = 0.912). No effects of primary medication or years since diagnosis (R-UPSIT®, p = 0.147; WETT®, p = 0.935) were found. Weak correlations were present between R-UPSIT® and WETT® scores for both control (r=0.187, p < 0.0001) and WD (r=0.237) subjects, although the latter correlation did not reach the 0.05 α level (p = 0.084). CONCLUSION: Although WD negatively impacts smell function, taste is spared. Research is needed to understand the pathophysiologic mechanisms responsible for this divergence.

Sniffing out meaning: Chemosensory and semantic neural network changes in sommeliers.

Wine tasting is a very complex process that integrates a combination of sensation, language, and memory. Taste and smell provide perceptual information that, together with the semantic narrative that converts flavor into words, seem to be processed differently between sommeliers and naïve wine consumers. We investigate whether sommeliers' wine experience shapes only chemosensory processing, as has been previously demonstrated, or if it also modulates the way in which the taste and olfactory circuits interact with the semantic network. Combining diffusion-weighted images and fMRI (activation and connectivity) we investigated whether brain response to tasting wine differs between sommeliers and nonexperts (1) in the sensory neural circuits representing flavor and/or (2) in the neural circuits for language and memory. We demonstrate that training in wine tasting shapes the microstructure of the left and right superior longitudinal fasciculus. Using mediation analysis, we showed that the experience modulates the relationship between fractional anisotropy and behavior: the higher the fractional anisotropy the higher the capacity to recognize wine complexity. In addition, we found functional differences between sommeliers and naïve consumers affecting the flavor sensory circuit, but also regions involved in semantic operations. The former reflects a capacity for differential sensory processing, while the latter reflects sommeliers' ability to attend to relevant sensory inputs and translate them into complex verbal descriptions. The enhanced synchronization between these apparently independent circuits suggests that sommeliers integrated these descriptions with previous semantic knowledge to optimize their capacity to distinguish between subtle differences in the qualitative character of the wine.