Propagating and banking genetically diverse human sapovirus strains using a human duodenal cell line: investigating antigenic differences between strains.

There are four genogroups and 18 genotypes of human sapoviruses (HuSaVs) responsible for acute gastroenteritis. To comprehend their antigenic and virological differences, it is crucial to obtain viral stocks of the different strains. Previously, we utilized the human duodenum-derived cell line HuTu80, and glycocholate, a conjugated bile acid, to replicate and propagate GI.1, GI.2, and GII.3 HuSaVs (H. Takagi et al., Proc Natl Acad Sci U S A 117:32078-32085, 2020, https://10.1073/pnas.2007310117). First, we investigated the impact of HuTu80 passage number on HuSaV propagation. Second, we demonstrated that taurocholate improved the initial replication success rate and viral RNA levels in fecal specimens relative to glycocholate. By propagating 15 HuSaV genotypes (GI.1-7, GII.1-5, -8, and GV.1-2) and accomplishing preparation of viral stocks containing 1.0 × 109 to 3.4 × 1011 viral genomic copies/mL, we found that all strains required bile acids for replication, with GII.4 showing strict requirements for taurocholate. The deduced VP1 sequences of the viruses during the scale-up of serial passaged virus cultures were either identical or differed by only two amino acids from the original sequences in feces. In addition, we purified virions from nine strains of different genotypes and used them as immunogens for antiserum production. Enzyme-linked immunosorbent assays (ELISAs) using rabbit and guinea pig antisera for each of the 15 strains of different genotypes revealed distinct antigenicity among the propagating viruses across genogroups and differences between genotypes. Acquisition of biobanked viral resources and determination of key culture conditions will be valuable to gain insights into the common mechanisms of HuSaV infection. IMPORTANCE: The control of human sapovirus, which causes acute gastroenteritis in individuals of all ages, is challenging because of its association with outbreaks similar to those caused by human norovirus. The establishment of conditions for efficient viral propagation of various viral strains is essential for understanding the infection mechanism and identifying potential control methods. In this study, two critical factors for human sapovirus propagation in a conventional human duodenal cell line were identified, and 15 strains of different genotypes that differed at the genetic and antigenic levels were isolated and used to prepare virus stocks. The preparation of virus stocks has not been successful for noroviruses, which belong to the same family as sapoviruses. Securing virus stocks of multiple human sapovirus strains represents a significant advance toward establishing a reliable experimental system that does not depend on limited virus-positive fecal material.

Deep learning-based segmentation of subcellular organelles in high-resolution phase-contrast images.

Although quantitative analysis of biological images demands precise extraction of specific organelles or cells, it remains challenging in broad-field grayscale images, where traditional thresholding methods have been hampered due to complex image features. Nevertheless, rapidly growing artificial intelligence technology is overcoming obstacles. We previously reported the fine-tuned apodized phase-contrast microscopy system to capture high-resolution, label-free images of organelle dynamics in unstained living cells (Shimasaki, K. et al. (2024). Cell Struct. Funct., 49: 21-29). We here showed machine learning-based segmentation models for subcellular targeted objects in phase-contrast images using fluorescent markers as origins of ground truth masks. This method enables accurate segmentation of organelles in high-resolution phase-contrast images, providing a practical framework for studying cellular dynamics in unstained living cells.Key words: label-free imaging, organelle dynamics, apodized phase contrast, deep learning-based segmentation.

A high-resolution phase-contrast microscopy system for label-free imaging in living cells.

Cell biologists have long sought the ability to observe intracellular structures in living cells without labels. This study presents procedures to adjust a commercially available apodized phase-contrast (APC) microscopy system for better visualizing the dynamic behaviors of various subcellular organelles in living cells. By harnessing the versatility of this technique to capture sequential images, we could observe morphological changes in cellular geometry after virus infection in real time without probes or invasive staining. The tune-up APC microscopy system is a highly efficient platform for simultaneously observing the dynamic behaviors of diverse subcellular structures with exceptional resolution.

The effect of multiband sequences on statistical outcome measures in functional magnetic resonance imaging using a gustatory stimulus.

Recent technical developments have led to the invention of multiband functional magnetic resonance imaging (fMRI) sequences that allow for faster sampling rates. However, some studies have highlighted problems with these sequences, leading to a decreased temporal signal-to-noise ratio (tSNR). In addition, this temporal noise may interfere with detecting reward-related responses in mesolimbic regions. The blood-oxygen-level-dependent signal utilized in the majority of fMRI measurements is relatively slow. Furthermore, the cerebral response to gustatory stimuli would also be relatively slow. Therefore, given the temporal noise issues with multiband sequences, it is unclear whether multiband sequences are necessary for fMRI studies using gustatory stimuli. We thus conducted an fMRI experiment using a gustatory stimulus to investigate the effects of multiband sequences and increased sampling rates on statistical outcome measures. A single-band sequence with a repetition time (TR) of 2 s of phantom fMRI data and gustatory fMRI data from the gustatory regions exhibited the highest tSNR, although the tSNR of this sequence of gustatory fMRI was not statistically different from tSNR of multiband sequences with a TR of 2 s in any of the selected region of interests. Conventional general linear model analysis of fMRI showed that single-band sequences are more advantageous than multiband sequences for detecting brain responses to gustatory stimuli in the primary gustatory cortex. In addition, a Bayesian data comparison showed that data derived from a single-band sequence with a TR of 2 s was optimal for inferring neuronal connectivity in gustatory processing. Therefore, a conventional single-band sequence with a TR of 2 s is more appropriate for fMRI with gustatory stimuli. Image acquisition sequences should be selected aligned with the study objectives and target brain regions.

Inhibition Mechanism of SARS-CoV-2 Infection by a Cholesterol Derivative, Nat-20(S)-yne.

The coronavirus disease 2019 (COVID-19) is caused by the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19, with the recurrent epidemics of new variants of SARS-CoV-2, remains a global public health problem, and new antivirals are still required. Some cholesterol derivatives, such as 25-hydroxycholesterol, are known to have antiviral activity against a wide range of enveloped and non-enveloped viruses, including SARS-CoV-2. At the entry step of SARS-CoV-2 infection, the viral envelope fuses with the host membrane dependent of viral spike (S) glycoproteins. From the screening of cholesterol derivatives, we found a new compound 26,27-dinorcholest-5-en-24-yne-3ß,20-diol (Nat-20(S)-yne) that inhibited the SARS-CoV-2 S protein-dependent membrane fusion in a syncytium formation assay. Nat-20(S)-yne exhibited the inhibitory activities of SARS-CoV-2 pseudovirus entry and intact SARS-CoV-2 infection in a dose-dependent manner. Among the variants of SARS-CoV-2, inhibition of infection by Nat-20(S)-yne was stronger in delta and Wuhan strains, which predominantly invade into cells via fusion at the plasma membrane, than in omicron strains. The interaction between receptor-binding domain of S proteins and host receptor ACE2 was not affected by Nat-20(S)-yne. Unlike 25-hydroxycholesterol, which regulates various steps of cholesterol metabolism, Nat-20(S)-yne inhibited only de novo cholesterol biosynthesis. As a result, plasma membrane cholesterol content was substantially decreased in Nat-20(S)-yne-treated cells, leading to inhibition of SARS-CoV-2 infection. Nat-20(S)-yne having a new mechanism of action may be a potential therapeutic candidate for COVID-19.

Short sleep duration and smoking initiation in university students: a retrospective cohort study.

PURPOSE: The aim of this study was to clarify an association between short sleep duration and smoking initiation. METHODS: Participants eligible for this retrospective cohort study were university students who were admitted to a single national university in Japan between 2007 and 2015. Baseline sleep duration and smoking status were measured using general questionnaires at health checkups at admission. During a 6-year observation period, smoking initiation was assessed using general questionnaires at annual health checkups. Cox proportional hazards models adjusted for clinically relevant factors were used to assess the association between sleep duration and smoking initiation. RESULTS: Of 17,493 men, including 540, 5,568, 8,458, 2,507, and 420 men with sleep duration of < 5, 5-6, 6-7, 7-8, and ≥ 8 h, respectively, smoking initiation was observed in 16.1%, 12.5%, 11.2%, 10.0%, and 11.7%, respectively, during a median observation period of 3.0 years. Men with shorter sleep duration were at a higher risk of smoking initiation (adjusted hazard ratio 1.49 [95% confidence interval 1.19-1.85], 1.11 [1.01-1.22], 1.00 [reference], 0.92 [0.80-1.06], and 1.00 [0.75-1.34], respectively). Of 8,880 women, including 267, 3,163, 4,220, and 1,230 women with sleep duration of < 5, 5-6, 6-7, and ≥ 7 h, respectively, smoking initiation was observed in 4.9%, 2.3%, 2.0%, and 2.2%, respectively, during a median observation period of 3.0 years. A similar dose dependent association was ascertained in women (2.50 [1.39-4.49], 1.18 [0.86-1.62], 1.00 [reference], and 1.22 [0.79-1.89], respectively). CONCLUSION: This study clarified that university students with short sleep duration were vulnerable to smoking initiation.

Food go/no-go training alters neural circuits for food evaluation for appetite reduction.

Food go/no-go training has been traditionally categorized as a type of inhibitory training that decreases the desire for high-calorie food consumption. This training requires participants to either respond or withhold their responses to presented items with go cues or food items with no-go cues, respectively. Recent findings have suggested that this training may devalue food items associated with no-go cues instead of facilitating inhibitory control, leading to reduced food consumption. We thus hypothesized that food go/no-go training would alter the brain response to food items with no-go cues in food evaluation regions. To examine this hypothesis, we conducted a repeated measures functional magnetic resonance imaging using food images in healthy participants, who underwent 3 weeks of food go/no-go training (n = 26) using high- and low-calorie food items paired with no-go cues (no-go food) and go cues (go food), respectively, and control training (n = 24). The food go/no-go training reduced the ratings for the desire to eat no-go foods and increased the ratings for go foods. The reduction in no-go food rating was positively associated with a decrease in daily snack intake. The neural responses in the food evaluation regions increased for go foods. Moreover, the functional connectivity of those regions was altered. The food go/no-go training did not decrease impulsivity traits or increase restrained eating, which are associated with inhibitory control. Overall, food go/no-go training influenced the brain regions associated with food evaluation, thus devaluating no-go foods and reducing the daily snack intake. Accordingly, food go/no-go training could promote healthier food choices.

Feasibility of preventing massive contrast media extravasation using a sensor device in contrast-enhanced CT: an observational study.

BACKGROUND: Recent guidelines recommend direct patient observation, pressure monitoring, and sensor devices to prevent extravasation during contrast media (CM) injection. However, it is impractical in terms of time and cost to install sensors for all patients. PURPOSE: To identify risk factors for CM extravasations during contrast-enhanced computed tomography (CECT) in a large population and to establish criteria for placing the sensor device on patients. MATERIAL AND METHODS: This retrospective study included 143,556 patients who underwent CECT at our hospital between April 2012 and July 2022. We performed multivariable logistic regression analysis between patients with (n = 350) and randomly selected patients without CM extravasation (n = 350). We investigated the percentage of patients with sensor devices and their sensitivity for detecting extravasation using receiver operating characteristic curve analysis. RESULTS: The extravasation rate was 0.27%. Multivariable logistic regression analysis showed that the injection rate (adjusted odds ratio [AOR] = 1.61, 95% confidence interval [CI] = 1.33-1.95: P <0.001), catheter gauge (AOR = 3.86, 95% CI = 1.92-7.76; P <0.001), the use of anticancer drugs (AOR = 1.81, 95% CI = 1.32-2.50; P <0.001), and existing catheters (AOR = 1.52, 95% CI = 1.10-2.11; P = 0.009) were significantly associated with extravasation. To achieve a sensitivity of 90%, 80%, 70%, 60%, and 50%, 80%, 65%, 50%, 40%, and 28% of all patients required the placement of a sensor device, respectively. CONCLUSION: Sensitivity analysis established criteria for effective placing sensor devices.

Respective Involvement of the Right Cerebellar Crus I and II in Syntactic and Semantic Processing for Comprehension of Language.

The right posterolateral portions of the cerebellum (crus-I/II) are involved in language processing. However, their functional role in language remains unknown. The cerebellum is hypothesized to acquire an internal model that is a functional copy of mental representations in the cerebrum and to contribute to cognitive function. In this research, based on the cerebellar internal model hypothesis, we conducted task-based and resting-state functional magnetic resonance imaging (fMRI) experiments to investigate the role of the cerebellum in the syntactic and semantic aspects of comprehension of sentences. In a syntactic task, participants read sentences with center-embedded hierarchical structures. The hierarchical level-dependent activity was found in the right crus-I as well as Broca's area (p < 0.05, voxel-based small volume correction (SVC)). In a semantic task, the participants read three types of sentences for investigation of sentence-level, phrase-level, and word-level semantic processing. The semantic level-dependent activity was found in the right crus-II as well as in the left anterior temporal lobe and the left angular gyrus (p < 0.05, voxel-based SVC). Moreover, the right crus-I/II showed significant activity when the cognitive load was high. Resting-state fMRI demonstrated intrinsic functional connectivity between the right crus-I/II and language-related regions in the left cerebrum (p < 0.05, voxel-based SVC). These findings suggest that the right crus-I and crus-II are involved, respectively, in the syntactic and semantic aspects of sentence processing. The cerebellum assists processing of language in the cerebrum when the cognitive load is high.

Establishment of measles virus receptor-expressing Vero cells lacking functional poliovirus receptors.

Global efforts are underway to eliminate measles and rubella, and active viral surveillance is the key to achieving this goal. In addition, the World Health Organization announced guidelines for handling materials potentially infectious for poliovirus (PV) to minimize the risk of PV reintroduction and to achieve PV eradication. To support global efforts, we established new PV-non-susceptible cell lines that are useful for the isolation of measles virus (MeV) and rubella virus (RuV) (Vero ΔPVR1/2 hSLAM+). In the cell lines, MeV and RuV replicated efficiently, with no concern regarding PV replication.

Daily fat intake is associated with basolateral amygdala response to high-calorie food cues and appetite for high-calorie food.

OBJECTIVES: Animal studies have indicated that fat intake mediates amygdala activation, which in turn promotes fat intake, while amygdala activation increases the preference for fat and leads to increased fat intake. However, the association among fat intake, amygdala activation, and appetite for high-calorie foods in humans remains unclear. Thus, to examine this association, we conducted a functional magnetic resonance imaging (fMRI) experiment. METHODS: Fifty healthy-weight adults (18 females; mean age: 22.9 ± 3.02 years) were included. Participants were shown images of high-calorie and low-calorie foods and were instructed to rate their desire to eat the food items during fMRI. All participants provided information on their daily fat intake using a self-reported questionnaire. Associations among fat intake, the desire to eat high-calorie or low-calorie food items, and amygdala responses to food items were examined. RESULTS: The basolateral amygdala (BLA) response was positively associated with fat intake ([x, y, z] = [24, -6, -16], z = 3.91, pFWE-corrected = 0.007) and the desire to eat high-calorie food items ([26, -4, -16], z = 3.75, pFWE-corrected = 0.010). Structural equation modeling showed that the desire for high-calorie food items was predicted by BLA response to high-calorie food items (p = 0.013, ß = 3.176), and BLA response was predicted by fat intake (p < 0.001, ß = 0.026). DISCUSSION: Fat intake influences BLA response to high-fat food, which in turn increases the desire to eat palatable high-fat food. This may lead to additional fat intake and increase the risk of weight gain.

Distinctive alterations in the mesocorticolimbic circuits in various psychiatric disorders.

AIM: Increasing evidence suggests that psychiatric disorders are linked to alterations in the mesocorticolimbic dopamine-related circuits. However, the common and disease-specific alterations remain to be examined in schizophrenia (SCZ), major depressive disorder (MDD), and autism spectrum disorder (ASD). Thus, this study aimed to examine common and disease-specific features related to mesocorticolimbic circuits. METHODS: This study included 555 participants from four institutes with five scanners: 140 individuals with SCZ (45.0% female), 127 individuals with MDD (44.9%), 119 individuals with ASD (15.1%), and 169 healthy controls (HC) (34.9%). All participants underwent resting-state functional magnetic resonance imaging. A parametric empirical Bayes approach was adopted to compare estimated effective connectivity among groups. Intrinsic effective connectivity focusing on the mesocorticolimbic dopamine-related circuits including the ventral tegmental area (VTA), shell and core parts of the nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) were examined using a dynamic causal modeling analysis across these psychiatric disorders. RESULTS: The excitatory shell-to-core connectivity was greater in all patients than in the HC group. The inhibitory shell-to-VTA and shell-to-mPFC connectivities were greater in the ASD group than in the HC, MDD, and SCZ groups. Furthermore, the VTA-to-core and VTA-to-shell connectivities were excitatory in the ASD group, while those connections were inhibitory in the HC, MDD, and SCZ groups. CONCLUSION: Impaired signaling in the mesocorticolimbic dopamine-related circuits could be an underlying neuropathogenesis of various psychiatric disorders. These findings will improve the understanding of unique neural alternations of each disorder and will facilitate identification of effective therapeutic targets.

Developing and validating a Japanese version of the Weight Self-Stigma Questionnaire.

PURPOSE: Weight bias internalization (WBI) is significantly associated with negative physiological and psychological consequences. Given its negative effects, appropriate measurement of WBI is required for weight management and mental and physical health in people with weight problems. One of the most reliable and frequently used questionnaires to assess WBI is the Weight Self-Stigma Questionnaire (WSSQ). However, a Japanese version of the WSSQ has not yet been developed. Thus, the current study aimed to develop a Japanese version of the WSSQ (WSSQ-J) and validate its psychometric properties in the Japanese context. METHODS: A total of 1454 Japanese participants (age 34.44 ± 6.92; male = 498) with diverse weight statuses (Body mass index: 21.44 ± 3.52, 13.79-41.40 kg/m2) completed an online survey for the WSSQ-J. The internal consistency of the WSSQ-J was estimated by calculating Cronbach's α. Confirmatory factor analysis (CFA) was then carried out to confirm that the factor structure of the WSSQ-J was the same as that of the subscales of the original WSSQ. RESULTS: The WSSQ-J had a Cronbach's α of 0.917, indicating good internal consistency. In CFA, the comparative fit index was 0.945, the root mean square error of approximation was 0.085, and the standardized root mean square residual was 0.040, indicating that the two-factor model showed satisfactory goodness-of-fit. CONCLUSION: This study replicated the original findings related to the WSSQ, showing that the WSSQ-J is a reliable WBI questionnaire consisting of two factors. Therefore, the WSSQ-J would be a reliable tool for assessing WBI among Japanese. LEVEL OF EVIDENCE: Level V, descriptive cross-sectional study.

The effect of acquisition duration on cerebral blood flow-based resting-state functional connectivity.

Resting-state functional connectivity (rs-FC) is widely used to examine the functional architecture of the brain, and the blood-oxygenation-level-dependent (BOLD) signal is often utilized for determining rs-FC. However, the BOLD signal is susceptible to various factors that have less influence on the cerebral blood flow (CBF). Therefore, CBF could comprise an alternative for determining rs-FC. Since acquisition duration is one of the essential parameters for obtaining reliable rs-FC, we investigated the effect of acquisition duration on CBF-based rs-FC to examine the reliability of CBF-based rs-FC. Nineteen participants underwent CBF scanning for a total duration of 50 min. Variance of CBF-based rs-FC within the whole brain and 13 large-scale brain networks at various acquisition durations was compared to that with a 50-min duration using the Levene's test. Variance of CBF-based rs-FC at any durations did not differ from that at a 50-min duration (p > .05). Regarding variance of rs-FC within each large-scale brain network, the acquisition duration required to obtain reliable estimates of CBF-based rs-FC was shorter than 10 min and varied across large-scale brain networks. Altogether, an acquisition duration of at least 10 min is required to obtain reliable CBF-based rs-FC. These results indicate that CBF-based resting-state functional magnetic resonance imaging (rs-fMRI) with more than 10 min of total acquisition duration could be an alternative method to BOLD-based rs-fMRI to obtain reliable rs-FC.

Asymmetric Synthesis of Isotopic Atropisomers based on ortho-CH3/CD3 Discrimination and Their Structural Properties.

N-C axially chiral 3-(2-trideuteriomethyl-4,6-dimethylphenyl)-2-ethylquinazolin-4-ones and 3-(2-trideuteriomethyl-4,6-dimethylphenyl)-2-(1-phenylpropan-2-yl)quinazolin-4-ones were prepared in high enantio- and diastereomeric purities (98% ee). These quinazolinone derivatives are isotopic atropisomers based on ortho-CH3/CD3 discrimination and were revealed to possess a slight optical rotation and high rotational stability.

Nutrient infusion evoked magnetic resonance imaging signal in the human hypothalamus.

BACKGROUND: The hypothalamus receives ingested nutrient information via ascending gut-related projections and plays a significant role in the regulation of food intake. Human neuroimaging studies have observed changes in the activity or connectivity of the hypothalamus in response to nutrient ingestion. However, previous neuroimaging studies have not yet assessed differences in temporal changes of hypothalamic responses to various nutrients in humans. Thus a repeated measures functional magnetic resonance imaging (fMRI) study using 30-min scans was designed to examine differences in hypothalamic responses to various nutrients. METHODS: In this study, 18 healthy adults (mean age, 22.4 years; standard deviation, 4.8; age range, 19-39 years; 11 males and seven females) underwent fMRI sessions. On the day of each session, one of the four solutions (200 ml of monosodium glutamate, glucose, safflower oil emulsion, or saline) was administered to participants while fMRI scanning. RESULTS: Infused amino acid and glucose, but not lipid emulsion, increased lateral hypothalamic responses as compared to a saline infusion ([x, y, z] = [4, -4, -10], z = 2.96). In addition, only hypothalamic responses to saline, but not those to the infusion of other nutrients, elicited a subjective sensation of hunger. CONCLUSION: These findings suggest that lateral hypothalamic responses to ingested nutrients may mediate homeostatic sensations in humans.

Triaging of COVID-19 patients using low dose chest CT: Incidence and factor analysis of lung involvement on CT images.

INTRODUCTION: Despite an increase in CT studies to evaluate patients with coronavirus disease 2019 (COVID-19), their indication in triage is not well-established. The purpose was to investigate the incidence of lung involvement and analyzed factors related to lung involvement on CT images for establishment of the indication for CT scans in the triaging of COVID-19 patients. METHODS: Included were 192 COVID-19 patients who had undergone CT scans and blood tests for triaging. Two radiologists reviewed the CT images and recorded the incidence of lung involvement. The prediction model for lung involvement on CT images using clinico-laboratory variables [age, gender, body mass index, oxygen saturation of the peripheral artery (SpO2), comorbidities, symptoms, and blood data] were developed by multivariate logistic regression with cross-validation. RESULTS: In 120 of the 192 patients (62.5%), CT revealed lung involvement. The patient age (odds ratio [OR]; 4.95, 95% confidence interval [CI]; 0.93-26.49), albumin (OR; 4.66, 95%CI; 1.37-15.84), lactate dehydrogenase (OR; 5.79, 95%CI; 1.43-23.38) and C-reactive protein (OR; 8.93, 95%CI; 4.13-19.29) were selected for the final prediction model for lung involvement on CT images. The cross-validated area under the receiver operating characteristics (ROC) curve was 0.83. CONCLUSIONS: The high incidence of lung involvement (62.5%) was confirmed on CT images. The proposed prediction model that includes the patient age, albumin, lactate dehydrogenase, and C-reactive protein may be useful for predicting lung involvement on CT images and may assist in deciding whether triaged COVID-19 patients should undergo CT.

Intermolecular Halogen Bond Detected in Racemic and Optically Pure N-C Axially Chiral 3-(2-Halophenyl)quinazoline-4-thione Derivatives.

The halogen bond has been widely used as an important supramolecular tool in various research areas. However, there are relatively few studies on halogen bonding related to molecular chirality. 3-(2-Halophenyl)quinazoline-4-thione derivatives have stable atropisomeric structures due to the rotational restriction around an N-C single bond. In X-ray single crystal structures of the racemic and optically pure N-C axially chiral quinazoline-4-thiones, we found that different types of intermolecular halogen bonds (C=S⋯X) are formed. That is, in the racemic crystals, the intermolecular halogen bond between the ortho-halogen atom and sulfur atom was found to be oriented in a periplanar conformation toward the thiocarbonyl plane, leading to a syndiotactic zig-zag array. On the other hand, the halogen bond in the enantiomerically pure crystals was oriented orthogonally toward the thiocarbonyl plane, resulting in the formation of a homochiral dimer. These results indicate that the corresponding racemic and optically pure forms in chiral molecules are expected to display different halogen bonding properties, respectively, and should be separately studied as different chemical entities.

Identification of an Amygdala-Thalamic Circuit That Acts as a Central Gain Mechanism in Taste Perceptions.

Peripheral sources of individual variation in taste intensity perception have been well described. The existence of a central source has been proposed but remains unexplored. Here we used functional magnetic resonance imaging in healthy human participants (20 women, 8 men) to evaluate the hypothesis that the amygdala exerts an inhibitory influence that affects the "gain" of the gustatory system during tasting. Consistent with the existence of a central gain mechanism (CGM), we found that central amygdala response was correlated with mean intensity ratings across multiple tastants. In addition, psychophysiological and dynamic causal modeling analyses revealed that the connection strength between inhibitory outputs from amygdala to medial dorsal and ventral posterior medial thalamus predicted individual differences in responsiveness to taste stimulation. These results imply that inhibitory inputs from the amygdala to the thalamus act as a CGM that influences taste intensity perception.SIGNIFICANCE STATEMENT Whether central circuits contribute to individual variation in taste intensity perception is unknown. Here we used functional magnetic resonance imaging in healthy human participants to identify an amygdala-thalamic circuit where network dynamics and connectivity strengths during tasting predict individual variation in taste intensity ratings. This finding implies that individual differences in taste intensity perception do not arise solely from variation in peripheral gustatory factors.

Dietary Restraint Related to Body Weight Maintenance and Neural Processing in Value-Coding Areas in Adolescents.

BACKGROUND: There is an alarming increase in the obesity prevalence among children in an environment of increasing availability of preprocessed high-calorie foods. However, some people maintain a healthy weight even in such obesogenic environments. This difference in body weight management could be attributed to individual differences in dietary restraint; however, its underlying neurocognitive mechanisms in adolescents remain unclear. OBJECTIVES: This study aimed to elucidate these neurocognitive mechanisms in adolescents by examining the relationships between dietary restraint and the food-related value-coding region located in the ventromedial prefrontal cortex (vmPFC). METHODS: The association between dietary restraint and BMI was tested using a multilinear regression analysis in a large early adolescent cohort (n = 2554; age, 12.2 ± 0.3 years; BMI, 17.9 ± 2.5 kg/m2; 1354 boys). Further, an fMRI experiment was designed to assess the association between the vmPFC response to food images and dietary restraint in 30 adolescents (age, 17.6 ± 1.9 years; BMI, 20.7 ± 2.2 kg/m2; 13 boys). Additionally, using 54 individuals from the cohort (age, 14.5 ± 0.6 years; BMI, 18.8 ± 2.6 kg/m2; 31 boys), we assessed the association between dietary restraint and intrinsic vmPFC-related functional connectivity. RESULTS: In the cohort, adolescents with increased dietary restraint showed a lower BMI (ß = -0.38; P < 0.001; B = -0.06; SE = 0.003). The fMRI results showed a decreased vmPFC response to high-calorie food were correlated with greater dietary restraint. Moreover, there was an association of attenuated intrinsic vmPFC-related functional connectivity in the superior and middle frontal gyrus and the middle temporal gyrus with greater dietary restraint. CONCLUSIONS: Our findings suggest that dietary restraint in adolescents could be a preventive factor for weight gain; its effect involves modulating the vmPFC, which is associated with food value coding.