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.

Odour-imagery ability is linked to food craving, intake, and adiposity change in humans.

It is well-known that food-cue reactivity (FCR) is positively associated with body mass index (BMI)1 and weight change2, but the mechanisms underlying these relationships are incompletely understood. One prominent theory of craving posits that the elaboration of a desired substance through sensory imagery intensifies cravings, thereby promoting consumption3. Olfaction is integral to food perception, yet the ability to imagine odours varies widely4. Here we test in a basic observational study whether this large variation in olfactory imagery drives FCR strength to promote adiposity in 45 adults (23 male). We define odour-imagery ability as the extent to which imagining an odour interferes with the detection of a weak incongruent odour (the 'interference effect'5). As predicted in our preregistration, the interference effect correlates with the neural decoding of imagined, but not real, odours. These perceptual and neural measures of odour imagery are in turn associated with FCR, defined by the rated craving intensity of liked foods and cue-potentiated intake. Finally, odour imagery exerts positive indirect effects on changes in BMI and body-fat percentage over one year via its influences on FCR. These findings establish odour imagery as a driver of FCR that in turn confers risk for weight gain.

Habitual daily intake of a sweet and fatty snack modulates reward processing in humans.

Western diets rich in fat and sugar promote excess calorie intake and weight gain; however, the underlying mechanisms are unclear. Despite a well-documented association between obesity and altered brain dopamine function, it remains elusive whether these alterations are (1) pre-existing, increasing the individual susceptibility to weight gain, (2) secondary to obesity, or (3) directly attributable to repeated exposure to western diet. To close this gap, we performed a randomized, controlled study (NCT05574660) with normal-weight participants exposed to a high-fat/high-sugar snack or a low-fat/low-sugar snack for 8 weeks in addition to their regular diet. The high-fat/high-sugar intervention decreased the preference for low-fat food while increasing brain response to food and associative learning independent of food cues or reward. These alterations were independent of changes in body weight and metabolic parameters, indicating a direct effect of high-fat, high-sugar foods on neurobehavioral adaptations that may increase the risk for overeating and weight gain.

Odor imagery but not perception drives risk for food cue reactivity and increased adiposity.

Mental imagery has been proposed to play a critical role in the amplification of cravings. Here we tested whether olfactory imagery drives food cue reactivity strength to promote adiposity in 45 healthy individuals. We measured odor perception, odor imagery ability, and food cue reactivity using self-report, perceptual testing, and neuroimaging. Adiposity was assessed at baseline and one year later. Brain responses to real and imagined odors were analyzed with univariate and multivariate decoding methods to identify pattern-based olfactory codes. We found that the accuracy of decoding imagined, but not real, odor quality correlated with a perceptual measure of odor imagery ability and with greater adiposity changes. This latter relationship was mediated by cue-potentiated craving and intake. Collectively, these findings establish odor imagery ability as a risk factor for weight gain and more specifically as a mechanism by which exposure to food cues promotes craving and overeating.

Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead. Cognition and Sensory Systems in Healthy and Diseased Subjects.

This article summarizes selected presentations from a session titled "Cognition and Sensory Systems in Healthy and Diseased Subjects", held to highlight and honor the work of Dr. Marilyn Jones-Gotman. The session was part of a two-day symposium, "Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead". The session presented research on epilepsy and sensory systems by colleagues and former trainees of Dr. Jones-Gotman. The extended summaries provide an overview of historical and current work in the neuropsychology of epilepsy, neuropsychological and neuroimaging approaches to understanding brain organization, sex differences in brain mechanisms underlying neurological disorders, dietary influences on brain function and cognition, and expertise in olfactory training and language experiences and their implications for brain organization and structure.

The Addiction-Susceptibility TaqIA/Ankk1 Controls Reward and Metabolism Through D2 Receptor-Expressing Neurons.

BACKGROUND: A large body of evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the TaqIA polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the ankyrin repeat and kinase domain containing 1 kinase (Ankk1) near the dopamine D2 receptor (D2R) gene. Homozygous expression of the A1 allele correlates with a 30% to 40% reduction of striatal D2R, a typical feature of addiction, overeating, and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior are unknown. METHODS: Here, we used transgenic and viral-mediated strategies to reveal the role of Ankk1 in the regulation of activity and functions of the striatum. RESULTS: We found that Ankk1 is preferentially enriched in striatal D2R-expressing neurons and that Ankk1 loss of function in the dorsal and ventral striatum leads to alteration in learning, impulsivity, and flexibility resembling endophenotypes described in A1 carriers. We also observed an unsuspected role of Ankk1 in striatal D2R-expressing neurons of the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with or without the A1 allele. CONCLUSIONS: Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for Ankk1 in the regulation of body metabolism.

Identification of a novel link between adiposity and visuospatial perception.

OBJECTIVE: Recent work has reported a negative association between BMI and performance on the Penn Line Orientation Task. To determine the reliability of this effect, a comprehensive assessment of visual function in individuals with healthy weight (HW) and those with overweight/obesity (OW/OB) was performed. METHODS: Visual acuity/contrast, Penn Line Orientation Task, and higher-order visuospatial function were measured in 80 (40 with HW, 40 with OW/OB) case-control study participants. Adiposity, fasting glucose, hemoglobin A1c, diet, physical activity, and heart rate variability were also assessed. A subgroup of 22 participants plus 5 additional participants (n = 27) underwent functional magnetic resonance imaging scanning. RESULTS: Compared with those with HW, individuals with OW/OB performed worse on tasks requiring judgments of line orientation. This effect was mediated by body fat percentage and was unrelated to other measures. Functional magnetic resonance imaging revealed a negative association between BMI and response in the primary visual cortex (V1) during line orientation judgment. Performance was unrelated to V1 response but positively correlated with response in a network of regions, including the lateral occipital cortex, when BMI was accounted for in the model. CONCLUSIONS: These results demonstrate a selective deficit in line orientation perception associated with adiposity and blunted activation in the V1 that cannot be attributed to visual acuity and does not generalize to other visuospatial tasks.

Olfactory decoding is positively associated with ad libitum food intake in sated humans.

The role of olfaction in eating behavior and body weight regulation is controversial. Here we reanalyzed data from a previous functional magnetic resonance imaging study to test whether central olfactory coding is associated with hunger/satiety state, food intake, and change in body weight over one year in healthy human adults. Since odor quality and category are coded across distributed neural patterns that are not discernible with traditional univariate analyses, we used multi-voxel pattern analyses to decode patterns of brain activation to food versus nonfood odors. We found that decoding accuracies in the piriform cortex and amygdala were greater in the sated compared to hungry state. Sated decoding accuracies in these and other regions were also associated with post-scan ad libitum food intake, but not with weight change. These findings demonstrate that the fidelity of olfactory decoding is influenced by meal consumption and is associated with immediate food intake, but not longer-term body weight regulation.

Dietary adaptation for weight loss maintenance at Yale (DAWLY): Protocol and predictions for a randomized controlled trial.

Background: Current therapies for obesity treatment are effective at producing short-term weight loss, but weight loss maintenance remains a significant challenge. Here we investigate the impact of pre-intervention dietary fat intake on the efficacy of a dietary supplement to support weight loss maintenance. Preclinical work demonstrates that a vagal afferent pathway critical for sensing dietary lipids is blunted by a high-fat diet (HFD), resulting in a reduced preference for a low-fat emulsion and severe blunting of the dopamine (DA) response to the gastric infusion of lipids. Infusion of the gut lipid messenger oleoylethanolamide (OEA), which is also depleted by HFD, immediately reverses this DA blunting and restores preference for the low-fat emulsion. Studies of OEA supplementation for weight loss in humans have had limited success. Given the strong effect of HFD on this pathway, we designed a study to test whether the efficacy of OEA as a weight loss treatment is related to pre-intervention habitual intake of dietary fat. Methods/Design: We employed a randomized, double-blind, placebo-controlled trial in which 100 adults with overweight/obesity (OW/OB) were randomized to receive either OEA or placebo daily for 16 months. Following a baseline evaluation of diet, metabolic health, adiposity, and brain response to a palatable an energy dense food, participants in both groups underwent a 4-month behavioral weight loss intervention (LEARN®) followed by a 1-year maintenance period. The study aims are to (1) determine if pre-intervention dietary fat intake moderates the ability of OEA to improve weight loss and weight loss maintenance after a gold standard behavioral weight loss treatment; (2) identify biomarkers that predict outcome and optimize a stratification strategy; and (3) test a model underlying OEA's effectiveness. Discussion: Focusing on interventions that target the gut-brain axis is supported by mounting evidence for the role of gut-brain signaling in food choice and the modulation of this circuit by diet. If successful, this work will provide support for targeting the gut-brain pathway for weight loss maintenance using a precision medicine approach that is easy and inexpensive to implement. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04614233].

Functional Connectivity of the Nucleus Accumbens and Changes in Appetite in Patients With Depression.

Importance: Major depressive disorder (MDD) is characterized by a substantial burden on health, including changes in appetite and body weight. Heterogeneity of depressive symptoms has hampered the identification of biomarkers that robustly generalize to most patients, thus calling for symptom-based mapping. Objective: To define the functional architecture of the reward circuit subserving increases vs decreases in appetite and body weight in patients with MDD by specifying their contributions and influence on disease biomarkers using resting-state functional connectivity (FC). Design, Setting, and Participants: In this case-control study, functional magnetic resonance imaging (fMRI) data were taken from the Marburg-Münster FOR 2107 Affective Disorder Cohort Study (MACS), collected between September 2014 and November 2016. Cross-sectional data of patients with MDD (n = 407) and healthy control participants (n = 400) were analyzed from March 2018 to June 2022. Main Outcomes and Measures: Changes in appetite during the depressive episode and their association with FC were examined using fMRI. By taking the nucleus accumbens (NAcc) as seed of the reward circuit, associations with opposing changes in appetite were mapped, and a sparse symptom-specific elastic-net model was built with 10-fold cross-validation. Results: Among 407 patients with MDD, 249 (61.2%) were women, and the mean (SD) age was 36.79 (13.4) years. Reduced NAcc-based FC to the ventromedial prefrontal cortex (vmPFC) and the hippocampus was associated with reduced appetite (vmPFC: bootstrap r = 0.13; 95% CI, 0.02-0.23; hippocampus: bootstrap r = 0.15; 95% CI, 0.05-0.26). In contrast, reduced NAcc-based FC to the insular ingestive cortex was associated with increased appetite (bootstrap r = -0.14; 95% CI, -0.24 to -0.04). Critically, the cross-validated elastic-net model reflected changes in appetite based on NAcc FC and explained variance increased with increasing symptom severity (all patients: bootstrap r = 0.24; 95% CI, 0.16-0.31; patients with Beck Depression Inventory score of 28 or greater: bootstrap r = 0.42; 95% CI, 0.25-0.58). In contrast, NAcc FC did not classify diagnosis (MDD vs healthy control). Conclusions and Relevance: In this study, NAcc-based FC reflected important individual differences in appetite and body weight in patients with depression that can be leveraged for personalized prediction. However, classification of diagnosis using NAcc-based FC did not exceed chance levels. Such symptom-specific associations emphasize the need to map biomarkers onto more confined facets of psychopathology to improve the classification and treatment of MDD.

Chronic pain precedes disrupted eating behavior in low-back pain patients.

Chronic pain is associated with anhedonia and decreased motivation. These behavioral alterations have been linked to alterations in the limbic brain and could explain the increased risk for obesity in pain patients. The mechanism of these behavioral changes and how they set in in relation to the development of chronic pain remain however poorly understood. Here we asked how eating behavior was affected in low-back pain patients before and after they transitioned to chronic pain, compared to patients whose pain subsided. Additionally, we assessed how the hedonic perception of fat-rich food, which is altered in chronic pain patients, related to the properties of the nucleus accumbens in this patients' population. We hypothesized that the accumbens would be directly implicated in the hedonic processing of fat-rich food in pain patients because of its well-established role in hedonic feeding and fat ingestion, and its emerging role in chronic pain. Accordingly, we used behavioral assays and structural brain imaging to test sub-acute back pain patients (SBP) and healthy control subjects at baseline and at approximately one-year follow-up. We also studied a sample of chronic low-back pain patients (CLBP) at one time point only. We found that SBP patients who recovered at follow-up (SBPr) and CLBP patients showed disrupted eating behaviors. In contrast, SBP patients who persisted in having pain at follow-up (SBPp) showed intact eating behavior. From a neurological standpoint, only SBPp and CLBP patients showed a strong and direct relationship between hedonic perception of fat-rich food and nucleus accumbens volume. This suggests that accumbens alterations observed in SBPp patients in previous works might protect them from hedonic eating disruptions during the early course of the illness. We conclude that disrupted eating behavior specifically sets in after pain chronification and is accompanied by structural changes in the nucleus accumbens.

Dietary lipids as regulators of reward processes: multimodal integration matters.

The abundance of energy-dense and palatable diets in the modern food environment tightly contributes to the obesity pandemic. The reward circuit participates to the regulation of body homeostasis by integrating energy-related signals with neural substrates encoding cognitive and motivational components of feeding behaviors. Obesity and lipid-rich diets alter dopamine (DA) transmission leading to reward dysfunctions and food overconsumption. Recent reports indicate that dietary lipids can act, directly and indirectly, as functional modulators of the DA circuit. This raises the possibility that nutritional or genetic conditions affecting 'lipid sensing' mechanisms might lead to maladaptations of the DA system. Here, we discuss the most recent findings connecting dietary lipid sensing with DA signaling and its multimodal influence on circuits regulating food-reward processes.

Fat and Carbohydrate Interact to Potentiate Food Reward in Healthy Weight but Not in Overweight or Obesity.

Prior work suggests that actual, but not estimated, energy density drives the reinforcing value of food and that energy from fat and carbohydrate can interact to potentiate reward. Here we sought to replicate these findings in an American sample and to determine if the effects are influenced by body mass index (BMI). Thirty participants with healthy weight (HW; BMI 21.92 ± 1.77; M ± SD) and 30 participants with overweight/obesity (OW/OB; BMI 29.42 ± 4.44) rated pictures of common American snacks in 120-kcal portions for liking, familiarity, frequency of consumption, expected satiety, healthiness, energy content, energy density, and price. Participants then completed an auction task where they bid for the opportunity to consume each food. Snacks contained either primarily carbohydrate, primarily fat, or roughly equal portions of fat and carbohydrate (combo). Replicating prior work, we found that participants with HW bid the most for combo foods in linear mixed model analyses. This effect was not observed among individuals with OW/OB. Additionally, in contrast with previous reports, our linear regression analyses revealed a negative relationship between the actual energy density of the snacks and bid amount that was mediated by food price. Our findings support altered macronutrient reinforcement in obesity and highlight potential influences of the food environment on the regulation of food reward.

Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection.

INTRODUCTION: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. METHODS AND FINDINGS: We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV-2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). CONCLUSIONS: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.

Further Evidence that Habitual Consumption of Sucralose with, but Not without, Carbohydrate Alters Glucose Metabolism.

In this letter, Dalenberg et al. provide a point-by-point response to the critique offered by Kahn and Sievenpiper. They also offer new evidence to support their original finding from a study they conducted in mice.

Post-traumatic olfactory loss and brain response beyond olfactory cortex.

Olfactory impairment after a traumatic impact to the head is associated with changes in olfactory cortex, including decreased gray matter density and decreased BOLD response to odors. Much less is known about the role of other cortical areas in olfactory impairment. We used fMRI in a sample of 63 participants, consisting of 25 with post-traumatic functional anosmia, 16 with post-traumatic hyposmia, and 22 healthy controls with normosmia to investigate whole brain response to odors. Similar neural responses were observed across the groups to odor versus odorless stimuli in the primary olfactory areas in piriform cortex, whereas response in the frontal operculum and anterior insula (fO/aI) increased with olfactory function (normosmia > hyposmia > functional anosmia). Unexpectedly, a negative association was observed between response and olfactory perceptual function in the mediodorsal thalamus (mdT), ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (pCC). Finally, connectivity within a network consisting of vmPFC, fO, and pCC could be used to successfully classify participants as having functional anosmia or normosmia. We conclude that, at the neural level, olfactory impairment due to head trauma is best characterized by heightened responses and differential connectivity in higher-order areas beyond olfactory cortex.

Development of MacroPics: A novel food picture set to dissociate the effects of carbohydrate and fat on eating behaviors.

Emerging evidence suggests that fat and carbohydrate interact to potentiate the reward value of food (DiFeliceantonio et al., 2018). The primary goal of the current study was to develop a novel picture set to facilitate research into the effects of macronutrient composition on food choice and eating behavior. Toward this aim, we developed "MacroPics." In Experiment 1, we photographed 120-kcal portions of 60 snack foods falling into one of the three macronutrient categories: (1) mostly carbohydrate, (2) mostly fat, or (3) a combination of fat and carbohydrate. Sixty-one participants rated the images for liking, familiarity, frequency of consumption, healthiness, estimated energy content (in kcal), and expected satiation. A subset of these images consisting of 36 items was then selected in an iterative process to minimize differences in ratings between the macronutrient categories while simultaneously ensuring similar within-category variability on a number of food characteristics (e.g., energy density, portion size, retail price) and visual properties (e.g., color, complexity, visual area). In Experiment 2, an independent sample of 67 participants rated the pictures of the final 36-item MacroPics. Both experiments reveal similar participant ratings across categories for item liking, familiarity, frequency, healthiness, and estimated energy content. Protein content was higher in the fat compared to the carbohydrate and combination categories, leading to higher ratings of estimated satiety and energy density for fatty foods. Item and macronutrient category characteristics of the final MacroPics set are reported.