Forming cognitive maps for abstract spaces: the roles of the human hippocampus and orbitofrontal cortex.

How does the human brain construct cognitive maps for decision-making and inference? Here, we conduct an fMRI study on a navigation task in multidimensional abstract spaces. Using a deep neural network model, we assess learning levels and categorized paths into exploration and exploitation stages. Univariate analyses show higher activation in the bilateral hippocampus and lateral prefrontal cortex during exploration, positively associated with learning level and response accuracy. Conversely, the bilateral orbitofrontal cortex (OFC) and retrosplenial cortex show higher activation during exploitation, negatively associated with learning level and response accuracy. Representational similarity analysis show that the hippocampus, entorhinal cortex, and OFC more accurately represent destinations in exploitation than exploration stages. These findings highlight the collaboration between the medial temporal lobe and prefrontal cortex in learning abstract space structures. The hippocampus may be involved in spatial memory formation and representation, while the OFC integrates sensory information for decision-making in multidimensional abstract spaces.

Body mass index, waist circumference, and mortality in subjects older than 80 years: a Mendelian randomization study.

BACKGROUND AND AIMS: Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. METHODS: A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS: During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. CONCLUSIONS: Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.

Neural substrates of affective temperaments: An intersubject representational similarity analysis to resting-state functional magnetic resonance imaging in nonclinical subjects.

Previous research has suggested that certain types of the affective temperament, including depressive, cyclothymic, hyperthymic, irritable, and anxious, are subclinical manifestations and precursors of mental disorders. However, the neural mechanisms that underlie these temperaments are not fully understood. The aim of this study was to identify the brain regions associated with different affective temperaments. We collected the resting-state functional magnetic resonance imaging (fMRI) data from 211 healthy adults and evaluated their affective temperaments using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire. We used intersubject representational similarity analysis to identify brain regions associated with each affective temperament. Brain regions associated with each affective temperament were detected. These regions included the prefrontal cortex, anterior cingulate cortex (ACC), precuneus, amygdala, thalami, hippocampus, and visual areas. The ACC, lingual gyri, and precuneus showed similar activity across several affective temperaments. The similarity in related brain regions was high among the cyclothymic, irritable, and anxious temperaments, and low between hyperthymic and the other affective temperaments. These findings may advance our understanding of the neural mechanisms underlying affective temperaments and their potential relationship to mental disorders and may have potential implications for personalized treatment strategies for mood disorders.

Heavy metals and metalloids exposure and liver function in Chinese adults - A nationally representative cross-sectional study.

BACKGROUND: In China, the effects of heavy metals and metalloids (HMMs) on liver health are not consistently documented, despite their prevalent environmental presence. OBJECTIVE: Our research assessed the association between HMMs and liver function biomarkers in a comprehensive sample of Chinese adults. METHODS: We analyzed data from 9445 participants in the China National Human Biomonitoring survey. Blood and urine were evaluated for HMM concentrations, and liver health was gauged using serum albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) metrics. Various statistical methods were employed to understand the relationship between 11 HMMs and liver function, adjusting for multiple factors. We also explored interactions with alcohol intake, gender, and age. RESULTS: Among HMMs, selenium in blood [weighted geometric mean (GM) = 95.56 µg/L] and molybdenum in urine (GM = 46.44 µg/L) showed the highest concentrations, while lead in blood (GM = 21.92 µg/L) and arsenic in urine (GM = 19.80 µg/L) had the highest levels among risk HMMs. Manganese and thallium consistently indicated potential risk factor to liver in both sample types, while selenium displayed potential liver protection. Blood HMM mixtures were negatively associated with ALB (ß = -0.614, 95% CI: -0.809, -0.418) and positively with AST (ß = 0.701, 95% CI: 0.290, 1.111). No significant associations were found in urine HMM mixtures. Manganese, tin, nickel, and selenium were notable in blood mixture associations, with selenium and cobalt being significant in urine. The relationship of certain HMMs varied based on alcohol consumption. CONCLUSION: This research highlights the complex relationship between HMM exposure and liver health in Chinese adults, particularly emphasizing metals like manganese, thallium, and selenium. The results suggest a need for public health attention to low dose HMM exposure and underscore the potential benefits of selenium for liver health. Further studies are essential to establish causality.

Mediating Role of Liver Dysfunction in the Association between Arsenic Exposure and Diabetes in Chinese Adults: A Nationwide Cross-Sectional Study of China National Human Biomonitoring (CNHBM) 2017-2018.

Inconsistent results have been reported regarding the association between low-to-moderate arsenic (As) exposure and diabetes. The effect of liver dysfunction on As-induced diabetes remains unclear. The cross-sectional study included 10,574 adults from 2017-2018 China National Human Biomonitoring. Urinary total As (TAs) levels were analyzed as markers of As exposure. Generalized linear mixed models and restricted cubic splines models were used to examine the relationships among TAs levels, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and diabetes prevalence. Mediating analysis was performed to assess whether liver dysfunction mediated the association between TAs and diabetes. Overall, the OR (95% CI) of diabetes in participants in the second, third, and fourth quartiles of TAs were 1.08 (0.88, 1.33), 1.17 (0.94, 1.45), and 1.52 (1.22, 1.90), respectively, in the fully adjusted models compared with those in the lowest quartile. Serum ALT was positively associated with TAs and diabetes. Additionally, mediation analyses showed that ALT mediated 4.32% of the association between TAs and diabetes in the overall population and 8.86% in the population without alcohol consumption in the past year. This study suggested that alleviating the hepatotoxicity of As could have implications for both diabetes and liver disease.

Dissociable contributions of the hippocampus and orbitofrontal cortex to representing task space in a social context.

The hippocampus (HC) and the orbitofrontal cortex (OFC) jointly encode a map-like representation of a task space to guide behavior. It remains unclear how the OFC and HC interact in encoding this map-like representation, though previous studies indicated that both regions have different functions. We acquired the functional magnetic resonance imaging data under a social navigation task in which participants interacted with characters in a two-dimensional "social space." We calculate the social relationships between the participants and characters and used a drift-diffusion model to capture the inner process of social interaction. Then we used multivoxel pattern analysis to explore the brain-behavior relationship. We found that (i) both the HC and the OFC showed higher activations during the selective trial than the narrative trial; (ii) the neural pattern of the right HC was associated with evidence accumulation during social interaction, and the pattern of the right lateral OFC was associated with the social relationship; (iii) the neural pattern of the HC can decode the participants choices, while the neural pattern of the OFC can decode the task information about trials. The study provided evidence for distinct roles of the HC and the OFC in encoding different information when representing social space.

The Relationship Between Physical Activity and All-Cause Mortality Among Older Adults - China, 1998-2018.

What is already known about this topic?: Previous research indicates that non-occupational physical activity can reduce mortality risk. Nevertheless, the relationship between occupational physical activity and health improvements has not been consistently established. What is added by this report?: The study found that regular exercise and leisure activities reduced the risk of all-cause mortality. However, the combination of exercise and leisure activities demonstrated more substantial benefits. Additionally, no meaningful association was identified between physical work and mortality risk within the older population. What are the implications for public health practice?: It may be beneficial to encourage older adults to engage in regular exercise and to partake actively in leisure activities. Combining these two elements might yield greater benefits than regular exercise alone.

Gray matter abnormalities in patients with major depressive disorder and social anxiety disorder: a voxel-based meta-analysis.

BACKGROUND: Major depressive and social anxiety disorders have a high comorbidity rate and similar cognitive patterns. However, their unique and shared neuroanatomical characteristics have not been fully identified. METHODS: Voxel-based morphometric studies comparing gray matter volume between patients with major depressive disorder/social anxiety disorder and healthy controls were searched using 4 electronic databases from the inception to March 2022. Stereotactic data were extracted and subsequently tested for convergence and differences using activation likelihood estimation. In addition, based on the result of the meta-analysis, behavioral analysis was performed to assess the functional roles of the regions affected by major depressive disorder and/or social anxiety disorder. RESULTS: In total, 34 studies on major depressive disorder with 2873 participants, and 10 studies on social anxiety disorder with 1004 subjects were included. Gray matter volume conjunction analysis showed that the right parahippocampal gyrus region, especially the amygdala, was smaller in patients compared to healthy controls. The contrast analysis of major depressive disorder and social anxiety disorder revealed lower gray matter volume in the right lentiform nucleus and medial frontal gyrus in social anxiety disorder and lower gray matter volume in the left parahippocampal gyrus in major depressive disorder. Behavioral analysis showed that regions with lower gray matter volume in social anxiety disorder are strongly associated with negative emotional processes. CONCLUSIONS: The shared and unique patterns of gray matter volume abnormalities in patients with major depressive and social anxiety disorder may be linked to the underlying neuropathogenesis of these mental illnesses and provide potential biomarkers. PROSPERO registration number: CRD42021277546.

Altered cortical myelin in the salience and default mode networks in major depressive disorder patients: A surface-based analysis.

INTRODUCTION: Evidence from previous genetic and post-mortem studies suggested that the myelination abnormality contributed to the pathogenesis of major depressive disorder (MDD). However, image-level alterations in cortical myelin content associated with MDD are still unclear. METHODS: The high-resolution T1-weighted (T1w) and T2-weighted (T2w) brain 3D structural images were obtained from 52 MDD patients and 52 healthy controls (HC). We calculated the vertex-based T1w/T2w ratio using the HCP structural pipelines to characterize individual cortical myelin maps at the fs_LR 32 k surface. We attempted to detect the clusters with significant differences in cortical myelin content between MDD and HC groups. We correlated the cluster-wise averaged myelin value and the clinical performances in MDD patients. RESULTS: The MDD patients showed significantly lower cortical myelin content in the cluster involving the left insula, orbitofrontal cortex, superior temporal cortex, transverse temporal gyrus, inferior frontal cortex, superior frontal gyrus, anterior cingulate cortex, precentral cortex, and postcentral cortex. The correlation analysis showed a significantly positive correlation between the cluster-wise cortical myelin content and the onset age of MDD patients. CONCLUSION: The MDD patients showed lower cortical myelin content in regions of the default mode network regions and salience network than healthy controls.

Multi-modal MRI measures reveal sensory abnormalities in major depressive disorder patients: A surface-based study.

BACKGROUND: Multi-modal magnetic resonance imaging (MRI) measures are supposed to be able to capture different brain neurobiological aspects of major depressive disorder (MDD). A fusion analysis of structural and functional modalities may better reveal the disease biomarker specific to the MDD disease. METHODS: We recruited 30 MDD patients and 30 matched healthy controls (HC). For each subject, we acquired high-resolution brain structural images and resting-state fMRI (rs-fMRI) data using a 3 T MRI scanner. We first extracted the brain morphometric measures, including the cortical volume (CV), cortical thickness (CT), and surface area (SA), for each subject from the structural images, and then detected the structural clusters showing significant between-group differences in each measure using the surface-based morphology (SBM) analysis. By taking the identified structural clusters as seeds, we performed seed-based functional connectivity (FC) analyses to determine the regions with abnormal FC in the patients. Based on a logistic regression model, we performed a classification analysis by selecting these structural and functional cluster-wise measures as features to distinguish the MDD patients from the HC. RESULTS: The MDD patients showed significantly lower CV in a cluster involving the right superior temporal gyrus (STG) and middle temporal gyrus (MTG), and lower SA in three clusters involving the bilateral STG, temporal pole gyrus, and entorhinal cortex, and the left inferior temporal gyrus, and fusiform gyrus, than the controls. No significant difference in CT was detected between the two groups. By taking the above-detected clusters as seeds to perform the seed-based FC analysis, we found that the MDD patients showed significantly lower FC between STG/MTG (CV's cluster) and two clusters located in the bilateral visual cortices than the controls. The logistic regression model based on the structural and functional features reached a classification accuracy of 86.7% (p < 0.001) between MDD and controls. CONCLUSION: The present study showed sensory abnormalities in MDD patients using the multi-modal MRI analysis. This finding may act as a disease biomarker distinguishing MDD patients from healthy individuals.

Leisure Activities, Genetic Risk, and Frailty: Evidence from the Chinese Adults Aged 80 Years or Older.

INTRODUCTION: About half of adults aged ≥80 years suffer from frailty. Exercise is considered effective in preventing frailty but may be inapplicable to adults aged ≥80 years due to physical limitations. As an alternative, we aimed to explore the association of leisure activities with frailty and identify potential interaction with established polygenic risk score (PRS) among adults aged ≥80 years. METHODS: Analyses were performed in a prospective cohort study of 7,471 community-living older adults aged ≥80 years who were recruited between 2002 and 2014 from 23 provinces in China. Leisure activity was assessed using a seven-question leisure activity index and frailty was defined as a frailty index ≥0.25 using a validated 39-item health-related scale. The PRS was constructed using 59 single-nucleotide polymorphisms associated with frailty in a subsample of 2,541 older adults. Cox proportional hazards models were used to explore the associations of leisure activities, PRS with frailty. RESULTS: The mean age of participants was 89.4 ± 6.6 years (range: 80-116). In total, 2,930 cases of frailty were identified during 42,216 person-years of follow-up. Each 1 unit increase in the leisure activity index was associated with 12% lower risk of frailty (hazard ratio: 0.88 [95% confidence interval, 0.85-0.91]). Participants with high genetic risk (PRS >2.47 × 10-4) suffered from 26% higher risk of frailty. Interaction between leisure activity and genetic risk was not observed. CONCLUSION: Evidence is presented for the independent association of leisure activities and genetic risk with frailty. Engagement in leisure activities is suggested to be associated with lower risk of frailty across all levels of genetic risk among adults aged ≥80 years.

Disrupted multi-scale topological organization of directed functional brain networks in patients with disorders of consciousness.

Disorders of consciousness are impaired states of consciousness caused by severe brain injuries. Previous resting-state functional magnetic resonance imaging studies have reported abnormal brain network properties at different topological scales in patients with disorders of consciousness by using graph theoretical analysis. However, it is still unclear how inter-regional directed propagation activities affect the topological organization of functional brain networks in patients with disorders of consciousness. To reveal the altered topological organization in patients with disorders of consciousness, we constructed whole-brain directed functional networks by combining functional connectivity analysis and time delay estimation. Then we performed graph theoretical analysis based on the directed functional brain networks at three topological scales, from the nodal scale, the resting-state network scale to the global scale. Finally, the canonical correlation analysis was used to determine the correlations between altered topological properties and clinical scores in patients with disorders of consciousness. At the nodal scale, we observed decreased in-degree and increased out-degree in the precuneus in patients with disorders of consciousness. At the resting-state network scale, the patients with disorders of consciousness showed reorganized motif patterns within the default mode network and between the default mode network and other resting-state networks. At the global scale, we found a lower global clustering coefficient in the patients with disorders of consciousness than in the controls. The results of the canonical correlation analysis showed that the abnormal degree and the disrupted motif were significantly correlated with the clinical scores of the patients with disorders of consciousness. Our findings showed that consciousness impairment can be revealed by abnormal directed connection patterns at multiple topological scales in the whole brain, and the disrupted directed connection patterns may serve as clinical biomarkers to assess the dysfunction of patients with disorders of consciousness.

Long-term fine particular exposure and incidence of frailty in older adults: findings from the Chinese Longitudinal Healthy Longevity Survey.

BACKGROUND: The association between fine particular matter (PM2.5) and frailty is less studied, and the national burden of PM2.5-related frailty in China is unknown. OBJECTIVE: To explore the association between PM2.5 exposure and incident frailty in older adults, and estimate the corresponding disease burden. DESIGN: Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. SETTING: Twenty-three provinces in China. SUBJECTS: A total of 25,047 participants aged ≥65-year-old. METHODS: Cox proportional hazards models were performed to evaluate the association between PM2.5 and frailty in older adults. A method adapted from the Global Burden of Disease Study was used to calculate the PM2.5-related frailty disease burden. RESULTS: A total of 5,733 incidents of frailty were observed during 107,814.8 person-years follow-up. A 10 µg/m3 increment of PM2.5 was associated with a 5.0% increase in the risk of frailty (Hazard Ratio = 1.05, 95% confidence interval = [1.03-1.07]). Monotonic, but non-linear exposure-response, relationships of PM2.5 with risk of frailty were observed, and slopes were steeper at concentrations >50 µg/m³. Considering the interaction between population ageing and mitigation of PM2.5, the PM2.5-related frailty cases were almost unchanged in 2010, 2020 and 2030, with estimations of 664,097, 730,858 and 665,169, respectively. CONCLUSIONS: This nation-wide prospective cohort study showed a positive association between long-term PM2.5 exposure and frailty incidence. The estimated disease burden indicated that implementing clean air actions may prevent frailty and substantially offset the burden of population ageing worldwide.

Serum per- and polyfluoroalkyl substances and abnormal lipid metabolism: A nationally representative cross-sectional study.

BACKGROUND: The associations of legacy per- and polyfluoroalkyl substances (PFAS) with lipid metabolism are controversial, and there is little information about the impact of emerging PFAS (6:2 Cl-PFESA) on lipid metabolism in China. OBJECTIVES: We aimed to explore the associations of legacy and emerging PFAS with lipid profiles and dyslipidemia in Chinese adults. METHODS: We included 10,855 Chinese participants aged 18 years and above in the China National Human Biomonitoring. The associations of 8 PFAS with 5 lipid profiles and 4 dyslipidemia were investigated using weighted multiple linear regression or weighted logistic regression, and the dose-response associations were investigated using restricted cubic spline model. RESULTS: Among the 8 PFAS, the concentration of PFOS was the highest, with a geometric mean of 5.15 ng/mL, followed by PFOA and 6:2 Cl-PFESA, which were 4.26 and 1.63 ng/mL, respectively. Legacy (PFOA, PFOS, PFUnDA) or emerging (6:2 Cl-PFESA) PFAS were associated with lipid profiles (TC, LDL-C, HDL-C, non HDL-C) and dyslipidemia (high LDL-C, high TC, low HDL-C), and their effects on TC were most obvious. TC concentration increased by 0.595 mmol/L in the highest quartile (Q4) of PFOS when compared with the lowest quartile (Q1), (95 % CI:0.396, 0.794). Restricted cubic spline models showed that PFAS are nonlinearly associated with TC, non HDL-C, LDL-C and HDL-C, and that the lipid concentrations tend to be stable when PFOS and PFOA were > 20 ng/mL well as when the 6:2 Cl-PFESA level was > 10 ng/mL. The positive associations between PFAS mixtures and lipid profiles were also significant. CONCLUSIONS: Single and mixed exposure to PFAS were positively associated with lipid profiles, and China's unique legacy PFAS substitutes (6:2 Cl-PFESA) contributed less to lipid profiles than legacy PFAS. In the future, cohort studies will be needed to confirm our findings.

Social navigation modulates the anterior and posterior hippocampal circuits in the resting brain.

Social navigation is a dynamic and complex process that requires the collaboration of multiple brain regions. However, the neural networks for navigation in a social space remain largely unknown. This study aimed to investigate the role of hippocampal circuit in social navigation from a resting-state fMRI data. Here, resting-state fMRI data were acquired before and after participants performed a social navigation task. By taking the anterior and posterior hippocampus (HPC) as the seeds, we calculated their connectivity with the whole brain using the seed-based static functional connectivity (sFC) and dynamic FC (dFC) approaches. We found that the sFC and dFC between the anterior HPC and supramarginal gyrus, sFC or dFC between posterior HPC and middle cingulate cortex, inferior parietal gyrus, angular gyrus, posterior cerebellum, medial superior frontal gyrus were increased after the social navigation task. These alterations were related to social cognition of tracking location in the social navigation. Moreover, participants who had more social support or less neuroticism showed a greater increase in hippocampal connectivity. These findings may highlight a more important role of the posterior hippocampal circuit in the social navigation, which is crucial for social cognition.

Mercury may reduce the protective effect of sea fish consumption on serum triglycerides levels in Chinese adults: Evidence from China National Human Biomonitoring.

Sea fish contain omega-3 polyunsaturated fatty acids (omega-3 PUFAs) which have been found to reduce triglyceride (TG) levels. However, sea fish may contain pollutants such as mercury which cause oxidative stress and increase TG levels. Therefore, the relationship between sea fish and TG remains unclear. We aimed to explore whether blood mercury (BHg) can affect the effect of sea fish consumption frequency on TG level among Chinese adults. A total of 10,780 participants were included in this study. BHg levels were measured using inductively coupled plasma mass spectrometry (ICP-MS). The associations of sea fish consumption frequency with BHg and TG levels as well as the association of BHg with TG levels were evaluated using multiple linear regression. Causal mediation analysis was used to evaluate the mediation effect of BHg levels on the association of sea fish consumption frequency with TG levels. The frequency of sea fish consumption showed a negative association with TG level. Compared with the participants who never ate sea fish, the TG level decreased by 0.193 mmol/L in those who ate sea fish once a week or more [ß (95%CI): -0.193 (-0.370, -0.015)]. Significant positive associations were observed of BHg with TG levels. With one unit increase of log2-transformed BHg, the change of TG level was 0.030 mmol/L [0.030 (0.009, 0.051)]. The association between sea fish consumption and TG was mediated by log2-transformed BHg [total effect = -0.037 (-0.074, -0.001); indirect effect = 0.009 (0.004, 0.015)], and the proportion mediated by log2-transformed BHg was 24.25%. BHg may reduce the beneficial effect of sea fish consumption frequency on TG levels among Chinese adults. Overall, sea fish consumption has more benefits than harms to TG.

Association of blood mercury exposure with depressive symptoms in the Chinese oldest old.

Depressive symptoms have a significant impact on the quality-of-life among the oldest old (aged ≥ 80 years) in the population. Current research on the association of blood mercury with depressive symptoms has mainly targeted the general population. However, it is unclear whether this association is present in the oldest old. We used data from the Healthy Aging and Biomarker Cohort Study carried out in 2017-2018, with 1154 participants aged ≥ 80 years eligible for analysis. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to detect blood mercury (Hg) levels, while the CES-D10 depression scale was used to assess depressive symptoms. The association between blood mercury levels and depressive symptoms was investigated using log-binomial and Poisson regression models. We also used restricted cubic splines (RCS) to assess the linear or nonlinear association of blood mercury with depressive symptoms scores. The 1154 participants ranged in age from 80 to 120 years, while the geometric mean of blood mercury concentration was 1.01 µg/L. After adjustment for covariates, log-binomial and Poisson regression analyses revealed a statistically significant, positive association of blood mercury with depressive symptoms. In comparison to the first tertile, the adjusted relative risks of blood mercury and the presence of depressive symptoms in the second and third tertiles were 1.55 (1.20-1.99) and 1.45 (1.11-1.90), respectively. The RCS model showed a linear association between blood mercury level and depressive symptoms scores. In conclusion, among the oldest old, we demonstrated that blood mercury levels were positively associated with depressive symptoms. Further surveys, especially cohort studies and clinical trials are needed to confirm these results.

Cadmium exposure is associated with testosterone levels in men: A cross-sectional study from the China National Human Biomonitoring.

BACKGROUND: Sex hormone disorders can cause adverse health consequences. While experimental data suggests that cadmium (Cd) disrupts the endocrine system, little is known about the link between Cd exposure and sex hormones in men. METHODS: We measured blood cadmium (B-Cd), urine cadmium (U-Cd), serum testosterone and serum estradiol in men aged ≥18 years old participating in the China National Human Biomonitoring program, from 2017 to 2018. Urine cadmium adjusted for creatinine (Ucr-Cd) and the serum testosterone to serum estradiol ratio (T/E2) were calculated. The association of Cd exposure to serum testosterone and T/E2 in men was analyzed with multiple linear regression models. RESULTS: Among Chinese men ≥18 years old, the weighted geometric mean (95% CI) of B-Cd and Ucr-Cd levels were 1.23 (1.12-1.35) µg/L and 0.53 (0.47-0.59) µg/g, respectively. The geometric means (95% CI) of serum testosterone and T/E2 were 18.56 (17.92-19.22) nmol/L and 143.86 (137.24-150.80). After adjusting for all covariates, each doubling of B-Cd level was associated with a 5.04% increase in serum testosterone levels (ß = 0.071; 95%CI: 0.057-0.086) and a 4.03% increase in T/E2 (ß = 0.057; 95%CI: 0.040-0.075); similar findings were found in Ucr-Cd. CONCLUSIONS: In Chinese men, Cd may be an endocrine disruptor, which is positively associated with serum testosterone and T/E2.

Neural correlates of transitive inference: An SDM meta-analysis on 32 fMRI studies.

Transitive inference (TI) is a critical capacity involving the integration of relevant information into prior knowledge structure for drawing novel inferences on unobserved relationships. To date, the neural correlates of TI remain unclear due to the small sample size and heterogeneity of various experimental tasks from individual studies. Here, the meta-analysis on 32 fMRI studies was performed to detect brain activation patterns of TI and its three paradigms (spatial inference, hierarchical inference, and associative inference). We found the hippocampus, prefrontal cortex (PFC), putamen, posterior parietal cortex (PPC), retrosplenial cortex (RSC), supplementary motor area (SMA), precentral gyrus (PreCG), and median cingulate cortex (MCC) were engaged in TI. Specifically, the RSC was implicated in the associative inference, whereas PPC, SMA, PreCG, and MCC were implicated in the hierarchical inference. In addition, the hierarchical inference and associative inference both evoked activation in the hippocampus, medial PFC, and PCC. Although the meta-analysis on spatial inference did not generate a reliable result due to insufficient amount of investigations, the present work still offers a new insight for better understanding the neural basis underlying TI.

Brain activation elicited by acute stress: An ALE meta-analysis.

Stress abounds in daily life and is closely related to psychiatric disease. Less is known about the neural basis for the gender differences in stress, and the common and specific neural mechanism for physiological and psychosocial stress. The current study obtained 141 stress-oriented neuroimaging experiments from 126 eligible articles and sorted them into nine types of neuroimaging datasets based on the combination of stress (general, physiological or psychosocial) and gender (overall, male or female). An activation likelihood estimation (ALE) meta-analysis was conducted on each dataset to detect the spatial convergence of activations. A hierarchical clustering analysis was also conducted to uncover the relationship between the stress-induced paradigms and spatial distribution of brain activations. We found that the physiological stress and psychosocial stress showed common activation in the bilateral anterior insula and brainstem, but different activation likelihood in the bilateral insula, thalami, middle cingulate cortex, left fusiform gyri, and left amygdala. Men were more likely to activate the bilateral thalami during physiological stress, whereas women were more likely to activate the left amygdala during psychosocial stress. The activation patterns are more consistent among different physiological stress paradigms than psychosocial stress paradigms. Our results suggest that physiological stress and psychosocial stress activate common brain regions for movement and attentional regulation but different brain regions for sensory and affective processing.