Opposite changes in morphometric similarity of medial reward and lateral non-reward orbitofrontal cortex circuits in obesity.

Obesity has a profound impact on metabolic health thereby adversely affecting brain structure and function. However, the majority of previous studies used a single structural index to investigate the link between brain structure and body mass index (BMI), which hinders our understanding of structural covariance between regions in obesity. This study aimed to examine the relationship between macroscale cortical organization and BMI using novel morphometric similarity networks (MSNs). The individual MSNs were first constructed from individual eight multimodal cortical morphometric features between brain regions. Then the relationship between BMI and MSNs within the discovery sample of 434 participants was assessed. The key findings were further validated in an independent sample of 192 participants. We observed that the lateral non-reward orbitofrontal cortex (lOFC) exhibited decoupling (i.e., reduction in integration) in obesity, which was mainly manifested by its decoupling with the cognitive systems (i.e., DMN and FPN) while the medial reward orbitofrontal cortex (mOFC) showed de-differentiation (i.e., decrease in distinctiveness) in obesity, which was mainly represented by its de-differentiation with the cognitive and attention systems (i.e., DMN and VAN). Additionally, the lOFC showed de-differentiation with the visual system in obesity, while the mOFC showed decoupling with the visual system and hyper-coupling with the sensory-motor system in obesity. As an important first step in revealing the role of underlying structural covariance in body mass variability, the present study presents a novel mechanism that underlies the reward-control interaction imbalance in obesity, thus can inform future weight-management approaches.

Individualized morphometric similarity predicts body mass index and food approach behavior in school-age children.

Childhood obesity is associated with alterations in brain structure. Previous studies generally used a single structural index to characterize the relationship between body mass index(BMI) and brain structure, which could not describe the alterations of structural covariance between brain regions. To cover this research gap, this study utilized two independent datasets with brain structure profiles and BMI of 155 school-aged children. Connectome-based predictive modeling(CPM) was used to explore whether children's BMI is reliably predictable by the novel individualized morphometric similarity network(MSN). We revealed the MSN can predict the BMI in school-age children with good generalizability to unseen dataset. Moreover, these revealed significant brain structure covariant networks can further predict children's food approach behavior. The positive predictive networks mainly incorporated connections between the frontoparietal network(FPN) and the visual network(VN), between the FPN and the limbic network(LN), between the default mode network(DMN) and the LN. The negative predictive network primarily incorporated connections between the FPN and DMN. These results suggested that the incomplete integration of the high-order brain networks and the decreased dedifferentiation of the high-order networks to the primary reward networks can be considered as a core structural basis of the imbalance between inhibitory control and reward processing in childhood obesity.

Multivariate resting-state functional connectomes predict and characterize obesity phenotypes.

The univariate obesity-brain associations have been extensively explored, while little is known about the multivariate associations between obesity and resting-state functional connectivity. We therefore utilized machine learning and resting-state functional connectivity to develop and validate predictive models of 4 obesity phenotypes (i.e. body fat percentage, body mass index, waist circumference, and waist-height ratio) in 3 large neuroimaging datasets (n = 2,992). Preliminary evidence suggested that the resting-state functional connectomes effectively predicted obesity/weight status defined by each obesity phenotype with good generalizability to longitudinal and independent datasets. However, the differences between resting-state functional connectivity patterns characterizing different obesity phenotypes indicated that the obesity-brain associations varied according to the type of measure of obesity. The shared structure among resting-state functional connectivity patterns revealed reproducible neuroimaging biomarkers of obesity, primarily comprising the connectomes within the visual cortex and between the visual cortex and inferior parietal lobule, visual cortex and orbital gyrus, and amygdala and orbital gyrus, which further suggested that the dysfunctions in the perception, attention and value encoding of visual information (e.g. visual food cues) and abnormalities in the reward circuit may act as crucial neurobiological bases of obesity. The recruitment of multiple obesity phenotypes is indispensable in future studies seeking reproducible obesity-brain associations.

Harsh, unpredictable childhood environments are associated with inferior frontal gyrus connectivity and binge eating tendencies in late adolescents.

Harsh, unpredictable childhood environments (HUCE) are associated with obesity older in life, but knowledge of how HUCE affect binge eating tendencies is lacking. Five hundred and one late adolescents aged 16-22 were recruited to finish resting state functional magnetic resonance imaging scan, behavioral measures including retrospective recall of childhood environmental harshness and unpredictability, binge eating tendencies and demographics. Three hundred and seventy-six of participants further completed the computerized visual probe task designed to evaluate attentional engagement towards high and low calorie food. As right inferior frontal gyrus (IFG) was the key nodes that related to both early life adversity and binge eating tendencies, it was treated as the interest region in the dynamic functional connectivity analyses. Results found that HUCE are associated with significant but modest decreases in connectivity of right inferior frontal gyrus (IFG)- bilateral medial frontal gyrus, right IFG - bilateral inferior parietal lobule (IPL), and right IFG - left superior frontal gyrus connectivity, as well as attentional engagement to high-calorie food and binge eating tendencies. A machine-learning method named linear support vector regression (SVR) and leave one out cross-validation (LOOCV) procedure used to examine the robustness of the brain-behavior relationship further confirm the findings. Mediation analyses suggested that right IFG - left IPL connectivity mediates the association of HUCE and binge eating tendencies. Findings suggest right IFG - left IPL connectivity may serve as a crucial neurobiological underpinning of HUCE to regulate binge eating behaviors. As such, these results contribute to a novel perspective and hypotheses in elucidating developmental neuro-mechanisms related to binge eating.

Connectome-based prediction of eating disorder-associated symptomatology.

BACKGROUND: Despite increasing knowledge on the neuroimaging patterns of eating disorder (ED) symptoms in non-clinical populations, studies using whole-brain machine learning to identify connectome-based neuromarkers of ED symptomatology are absent. This study examined the association of connectivity within and between large-scale functional networks with specific symptomatic behaviors and cognitions using connectome-based predictive modeling (CPM). METHODS: CPM with ten-fold cross-validation was carried out to probe functional networks that were predictive of ED-associated symptomatology, including body image concerns, binge eating, and compensatory behaviors, within the discovery sample of 660 participants. The predictive ability of the identified networks was validated using an independent sample of 821 participants. RESULTS: The connectivity predictive of body image concerns was identified within and between networks implicated in cognitive control (frontoparietal and medial frontal), reward sensitivity (subcortical), and visual perception (visual). Crucially, the set of connections in the positive network related to body image concerns identified in one sample was generalized to predict body image concerns in an independent sample, suggesting the replicability of this effect. CONCLUSIONS: These findings point to the feasibility of using the functional connectome to predict ED symptomatology in the general population and provide the first evidence that functional interplay among distributed networks predicts body shape/weight concerns.

Altered effective connectivity between reward and inhibitory control networks in people with binge eating episodes: A spectral dynamic causal modeling study.

BACKGROUND: Converging evidence points to the crucial role of brain connectivity involved in aberrant behavioral control and reward reactivity in the onset and maintenance of binge eating. However, the directional interaction pattern between brain's reward and inhibitory control systems in people with binge eating episodes is largely unknown. METHODS: Resting-state fMRI data were collected from 36 adults with binge eating episodes (age: 19.05 ± 0.90) and 36 well-matched controls (age: 18.88 ± 0.78). We applied spectral dynamic causal modeling approach to estimate effective connectivity of the executive control network (ECN) and reward network (RN) with 15 predefined regions of interest, and investigate the between-group differences in directional connectivity. RESULTS: Compared with controls, the positive connections within the ECN were significantly strengthened in individuals with binge eating episodes, while the negative connections from the ECN to RN and from the RN to ECN were significantly weakened. In adults with binge eating episodes, the RN→ECN connectivity was positively related to binge frequency even controlling for age, sex, and body mass index. CONCLUSION: This study represents an important first step in addressing the role of directional integration between reward and inhibitory control networks in binge eating, and provides novel evidence that the ability of people with binge eating episodes to maintain a balance between inhibitory control and reward reactivity is decreased, as reflected by diminished bidirectional negative effects of prefrontal-subcortical circuitry at rest.

Social support and overeating in young women: The role of altering functional network connectivity patterns and negative emotions.

Research suggests that social support has a protective effect on emotional health and emotionally induced overeating. Women are especially more sensitive to benefits from social support when facing eating problems. Although it has been demonstrated that social support can affect the neural processes of emotion regulation and reward perception, it is unclear how social support alters synergistic patterns in large-scale brain networks associated with negative emotions and overeating. We used a large sample of young women aged 17-22 years (N = 360) to examine how social support influences the synchrony of five intrinsic networks (executive control network [ECN], default mode network, salience network [SN], basal ganglia network, and precuneus network [PN]) and how these networks influence negative affect and overeating. Additionally, we explored these analyses in another sample of males (N = 136). After statistically controlling for differences in age and head movement, we observed significant associations of higher levels of social support with increased intra- and inter-network functional synchrony, particularly for ECN-centered network connectivity. Subsequent chain-mediated analyses showed that social support predicted overeating through the ECN-SN and ECN-PN network connectivity and negative emotions. However, these results were not found in men. These findings suggest that social support influences the synergistic patterns within and between intrinsic networks related to inhibitory control, emotion salience, self-referential thinking, and reward sensitivity. Furthermore, they reveal that social support and its neural markers may play a key role in young women's emotional health and eating behavior.

Application of computerized cognitive test battery in major depressive disorder: a narrative literature review.

BACKGROUND: Major depressive disorder (MDD) is a chronic and debilitating relapsing-remitting mood disorder, characterized by psychological, cognitive, and behavioral disturbances. The assessment of cognitive dysfunction in individuals with MDD has increasingly become a topic of concern in recent years. AIMS: To pool and compare the characteristics of various cognition evaluation tools. METHOD: Overview of recent research in application of computerized cognitive test battery in MDD. RESULTS: With recent technological advances in mobile health technologies and the ubiquity of smartphones, the use of traditional tools is no longer sufficient to monitor the dynamic changes of an individual's cognitive performance, which may be influenced by many factors, including, but not limited to, disease course and medications. Computerized tests have many advantages over traditional neuropsychological testing, chiefly in terms of time and cost savings, accurate recording of multiple response components, and the ability to automatically store and compare performance between testing sessions. In the following review, we summarized cognitive impairment characteristics of MDD, introduced traditional assessment tools of cognitive function in MDD, and reviewed the development of the current computerized cognitive test batteries for MDD. The comparisons among cognitive function evaluation tools were also performed. CONCLUSIONS: It is our belief that the improvement of existing novel computerized cognitive test batteries, the development of more comprehensive and easy-to-operate scales, verification techniques and multiple follow-up surveys among large sample populations may provide valuable clues for the evaluation and tracking of cognitive function in individuals with MDD.

Gray matter volume and functional connectivity underlying binge eating in healthy children.

PURPOSE: As a maladaptive disordered eating behavior, binge eating (BE) onset has been reported in children as young as eight years old and is linked with a range of negative psychological consequences. However, previous neuroimaging research of BE has mainly focused on adults in clinical conditions, and little is known about the potential neurostructural and neurofunctional bases of BE in healthy children. METHODS: In this study, we examined these issues in 76 primary school students (mean age = 9.86 years) using voxel-based morphometry and resting-state functional connectivity (rsFC) approaches. RESULTS: After controlling for age, sex, and total intracranial volume/head motion, we observed that higher levels of BE were correlated with greater gray matter volumes (GMV) in the left fusiform and right insula and weaker rsFC between the right insula and following three regions: right orbital frontal cortex, left cingulate gyrus, and left superior frontal gyrus. No significant associations were observed between BE and regional white matter volume. Significant sex differences were found only in the relationship between BE and GMV in the left fusiform. Furthermore, the GMV- and rsFC-based predictive models (a machine-learning method) achieved significant correlations between the actual and predicted BE values, demonstrating the robustness of our findings. CONCLUSION: The present study provides novel evidence for the brain structural and functional substrates of children's BE, and further reveals that the weakened communication between core regions associated with negative affectivity, reward responsivity, and executive function is strongly related to dysregulated eating. LEVEL OF EVIDENCE: Level V, descriptive study.

Altered connectivity patterns of medial and lateral orbitofrontal cortex underlie the severity of bulimic symptoms.

Objective: Compared to clinical bulimia nervosa, sub-threshold bulimic symptoms are becoming more prevalent in non-clinical or general population, which is repeatedly linked with the connectivity in orbitofrontal cortex (OFC), including functionally heterogeneous the medial and lateral OFC (mOFC; lOFC). However, the specific connectivity patterns of the mOFC and lOFC in individuals with severe or mild bulimic symptoms (SB; MB) remain poorly understood. Methods: We first utilized resting-state functional connectivity (FC) and spectral dynamic causal modeling (spDCM) to investigate abnormal functional and effective connectivity (EC) of OFC subregions in adults with different severity of bulimic. The SB group (n = 21), MB group (n = 114), and healthy controls (HC, n = 91) underwent rs-fMRI scans. A generalized linear model was applied to determine the OFC-seeded whole-brain FC across the three groups. Subsequently, spDCM was used to estimate differences in EC among the three groups based on the FC results. Results: We observed a shared neural basis for SB and MB groups (i.e., weaker lOFC-superior parietal lobule connectivity), which may support the role of dysfunctional inhibitory control in general bulimic symptomatology. Whereas, SB group displayed greater lOFC-occipital pole connectivity than MB group, suggesting the specificity of the neural correlates of full-threshold/severe bulimia. The directional links from the mOFC to lOFC and amygdala could further explain the aberrant interactions of reward sensitivity with inhibitory control and homeostatic energy in sub-threshold/mild condition. Conclusion: The current study provides novel evidence that divergent connectivity patterns of the lOFC and mOFC may contribute to different severities of bulimia, which will expands our understanding of the neurobiological substrates underlying bulimia across a spectrum from healthy to unhealthy.

Connectivity-based neuromarker for children's inhibitory control ability and its relevance to body mass index.

Preserving a normal body mass index (BMI) is crucial for the healthy growth and development of children. As a core aspect of executive functions, inhibitory control plays a pivotal role in maintaining a normal BMI, which is key to preventing issues of childhood obesity. By studying individual variations in inhibitory control performance and its associated connectivity-based neuromarker in a sample of primary school students (N = 64; 9-12 yr), we aimed to unravel the pathway through which inhibitory control impacts children's BMI. Utilizing resting-state functional MRI scans and a connectivity-based psychometric prediction framework, we found that enhanced inhibitory control abilities were primarily associated with increased functional connectivity in brain structures vital to executive functions, such as the superior frontal lobule, superior parietal lobule, and posterior cingulate cortex. Conversely, inhibitory control abilities displayed a negative relationship with functional connectivity originating from reward-related brain structures, such as the orbital frontal and ventral medial prefrontal lobes. Furthermore, we revealed that both inhibitory control and its corresponding neuromarker can moderate the association between food-related delayed gratification and BMI in children. However, only the neuromarker of inhibitory control maintained its moderating effect on children's future BMI, as determined in the follow-up after one year. Overall, our findings shed light on the potential mechanisms of how inhibitory control in children impacts BMI, highlighting the utility of the connectivity-based neuromarker of inhibitory control in the context of childhood obesity.

Resting-state functional network connectivity underlying conscientiousness in school-aged children.

Conscientiousness is a personality trait that matures from early childhood to late adolescence, yet little is known about its underlying brain mechanisms during this period. To investigate this, our study examined the resting-state functional network connectivity (rsFNC) of 69 school-aged children (mean age = 10.12 years, range = 9-12) using a whole-brain region-of-interest (ROI) based analysis, based on functional magnetic resonance imaging (fMRI). The results indicated a positive association between conscientiousness and the rsFNC between the fronto-parietal network (FPN) and two brain networks: the somatosensory motor-hand network (SMHN) and the auditory network (AN). However, conscientiousness was negatively associated with the rsFNC between FPN and two other networks: the salience network (SN); the default mode network (DMN). Moreover, our results suggest that the FPN may play a hub role in the neural performance of children's conscientiousness. Intrinsic brain networks, particularly those involved in higher-order cognitive functions, impact children's conscientiousness. Therefore, FPN plays an important role in the development of children's personality, providing insight into the neural mechanisms underlying children's personality.

Structural and functional neural patterns among sub-threshold bulimia nervosa: Abnormalities in dorsolateral prefrontal cortex and orbitofrontal cortex.

BACKGROUND: Disordered eating behaviors are prevalent among youngsters and highly associated with dysfunction in neurocognitive systems. We aimed to identify the potential changes in individuals with bulimia symptoms (sub-BN) to generate insights to understand developmental pathophysiology of bulimia nervosa. METHODS: We investigated group differences in terms of degree centrality (DC) and gray matter volume (GMV) among 145 undergraduates with bulimia symptoms and 140 matched control undergraduates, with the secondary analysis of the whole brain connectivity in these regions of interest showing differences in static functional connectivity (FC). RESULTS: The sub-BN group exhibited abnormalities of the right dorsolateral prefrontal cortex and right orbitofrontal cortex in both GMV and DC, and displayed decreased FC between these regions and the precuneus. We also observed that sub-BN presented with reduced FC between the calcarine and superior temporal gyrus, middle temporal gyrus and inferior parietal gyrus. Additionally, brain-behavioral associations suggest a distinct relationship between these FCs and psychopathological symptoms in sub-BN group. CONCLUSIONS: Our study demonstrated that individuals with bulimia symptoms present with aberrant neural patterns that mainly involved in cognitive control and reward processing, as well as attentional and self-referential processing, which could provide important insights into the pathology of BN.

The Mediating Role of Sleep Quality in the Association Between Negative Affect and Cognitive Function Among Patients With Nasopharyngeal Carcinoma After Intensity-Modulated Radiotherapy.

BACKGROUND: Cognitive function impairment is a severe yet largely unrecognized adverse reaction among patients with nasopharyngeal carcinoma (NPC) following radiotherapy. OBJECTIVES: The aims of this study were to examine the level of cognitive function, explore the influencing factors of the cognitive function of NPC after intensity-modulated radiotherapy (IMRT), and identify the mediating role of sleep quality between negative affect and cognitive function. METHODS: In total, 200 patients with NPC after IMRT were recruited from a tertiary cancer center in Southern China between September 2020 and March 2021. Participants completed the demographic and disease-related questionnaire, Montreal Cognitive Assessment Scale, Profile of Mood States-Short Form, and Pittsburgh Sleep Quality Index. RESULTS: The mean Montreal Cognitive Assessment Scale scores were 24.42 after adjustment, with 54.5% of patients having cognitive function impairment. Education level, income, seeking rehabilitation knowledge, radiation dose, sleep quality, and negative affect entered the final regression model and explained 82.6% of cognitive function variance. The total and direct effects of negative affect and indirect effects via sleep quality on cognitive function were significant (P < .05). CONCLUSIONS: Clinicians should pay close attention to patients with poor educational levels, low income, and having difficulties seeking rehabilitation knowledge and patients who accept higher radiation doses. Improving their sleep quality and positive affect may contribute to preventing or reducing cognitive function impairment. IMPLICATIONS FOR PRACTICE: Clinical nurses should pay more attention to cognitive function among NPC patients after IMRT and take effective measures or interventions to prevent and reduce their cognitive function impairment.

The relationship between brain neural correlates, self-objectification, and interoceptive sensibility.

Interoceptive sensibility refers to the tendency to focus on internal bodily states and the capacity to detect them. As the subjective dimension of interoception, interoceptive sensibility plays a key role in individuals' health. Self-objectification, a process by which individuals tend to adopt a third-person's perspective of their physical self, leads to decreased interoceptive sensibility. However, few studies regarding the neural basis of interoceptive sensibility and the underlying mechanism of the relationship between self-objectification and interoceptive sensibility have been conducted. In this study, we assessed the resting-state brain activity (fractional amplitude of low-frequency fluctuation, fALFF) and connectivity (resting-state functional connectivity, RSFC) of 442 college students. Whole-brain correlation analyses revealed that a higher level of interoceptive sensibility was linked to higher fALFF in the right inferior frontal gyrus (IFG) and left cerebellum and to lower fALFF in the left paracentral lobule and left superior/middle temporal gyrus. Interoceptive sensibility also was negatively associated with the RSFC between the right IFG and the right secondary somatosensory cortex (S2) and the right IFG and the ventral premotor cortex (VPC). These brain regions and connections are mainly responsible for switching attention to internal/external information and processing body-related somatosensory as well as sensory information. Mediation analyses suggested that the fALFF of the right IFG and the RSFC of IFG-S2 and IFG-VPC mediated the relationship between self-objectification and interoceptive sensibility. Overall, these results suggest that the IFG may be the neural marker of interoceptive sensibility and reveal several potential mediation models of the relationship between brain neural correlates and self-objectification and interoceptive sensibility.

Associations of harsh, unpredictable environment, amygdala connectivity and overeating for children.

OBJECTIVE: In harsh and unpredictable environments, individuals tend to engage in activities that yield immediate rewards as delayed benefits can be unavailable. Substantial evidence suggests that a harsh and unpredictable childhood environment is associated with overeating. However, the neuromechanisms underlying this association remain unclear. This study aimed to investigate amygdala connectivity in relation to environmental harshness and unpredictability (EHU) from an evolutionary perspective and examine their relationship with overeating in children. METHODS: Eighty-five children aged 8 to 12 years were scanned using a magnetic resonance imaging machine to assess resting-state functional connectivity (RSFC) of the two subregions of the amygdala (i.e., centromedial amygdala [CMA]; basolateral amygdala [BLA]). Self-reports of EHU and parental reports of overeating, including food responsiveness and enjoyment of food, were obtained cross-sectionally. Furthermore, findings indicated that children completed high- and low-calorie food portion choice tasks in the absence of hunger at 12 months of follow-up. RESULTS: EHU was positively associated with parental reports of overeating, including food responsiveness and enjoyment, as well as children's selection of high-calorie food portion sizes. Moreover, static RSFC analyses revealed that EHU was negatively associated with bilateral BLA-left inferior frontal gyrus (IFG) connectivity, while dynamic RSFC analyses found that EHU was negatively associated with right CMA, left inferior parietal lobule, and right CMA-right precuneus connectivity. Particularly, the left BLA-left IFG connectivity mediated the association between EHU and parental reports of food responsiveness. CONCLUSION: EHU was negatively associated with amygdala connectivity, which is implicated in the intrinsic processing of emotional regulation. Furthermore, deficits in emotional regulation resulted in increased energy intake. These insights provide a new perspective for understanding the developmental neuromechanisms underlying obesity.

Neural correlates of Type A personality: Type A personality mediates the association of resting-state brain activity and connectivity with eating disorder symptoms.

BACKGROUND: Type A personality (TAP) was characterized by impatience, competitiveness, aggressiveness, and hostility. Higher TAP was proved to be associated with more eating disorder symptoms (EDS). While little is known about the underlying neural substrates of TAP and how TAP is linked to EDS at the neural level. METHODS: To investigate the neural basis of TAP, we adopted fractional amplitude of low-frequency fluctuations (fALFF) and resting-state functional connectivity (RSFC) via resting-state functional magnetic resonance imaging (rs-fMRI) (N = 1620). Mediation models were examined to explore the relationship between TAP, EDS, and brain activity. RESULTS: TAP was associated with decreased fALFF in the left middle frontal gyrus (MFG) and increased fALFF in the left precentral gyrus (PreCG). Furthermore, TAP was positively correlated to RSFC between the left MFG and left inferior temporal gyrus (ITG) and between the left PreCG and right middle temporal gyrus (MTG). Mediation analysis showed TAP fully mediated the association of the left MFG activity, MFG-ITG connectivity, and PreCG-MTG connectivity with EDS. LIMITATIONS: The cross-sectional design of this study precludes us from specifying the causal relationship in the associations we observed. CONCLUSIONS: Our results suggested spontaneous activity in the left MFG and PreCG is associated with TAP, and even in general sample, people with higher TAP showed more EDS. The present study is the first to investigate the neurobiological underpinnings of TAP in a large sample and further offered new insights into the relation between TAP and EDS from a neural basis perspective.

Association Between Negative Affect and Perceived Mortality Threat During the COVID-19 Pandemic: The Role of Brain Activity and Connectivity.

The prevalence of the novel coronavirus (COVID-19) has been considered a major threat to physical and mental health around the world, causing great pressure and mortality threat to most people. The current study aimed to investigate the neurological markers underlying the relationship between perceived mortality threat (PMT) and negative affect (NA). We examined whether the regional amplitude of low-frequency fluctuations (ALFF) and resting-state functional connectivity (RSFC) before the COVID-19 outbreak (October 2019 to December 2019, wave 1) were predictive for NA and PMT during the mid-term of the COVID-19 pandemic (February 22 to 28, 2020, wave 2) among 603 young adults (age range 17-22, 70.8% females). Results indicated that PMT was associated with spontaneous activity in several regions (e.g., inferior temporal gyrus, medial occipital gyrus, medial frontal gyrus, angular gyrus, and cerebellum) and their RSFC with the distributed regions of the default mode network and cognitive control network. Furthermore, longitudinal mediation models showed that ALFF in the cerebellum, medial occipital gyrus, medial frontal gyrus, and angular gyrus (wave 1) predicted PMT (wave 2) through NA (wave 2). These findings revealed functional neural markers of PMT and suggest candidate mechanisms for explaining the complex relationship between NA and mental/neural processing related to PMT in the circumstance of a major crisis.

Association of loneliness and grey matter volume in the dorsolateral prefrontal cortex: the mediating role of interpersonal self-support traits.

As a social and public health concern, loneliness is associated with an abundance of negative life outcomes such as depressive symptomatology, mortality, and sleep disturbance. Nevertheless, the neural basis underlying loneliness remains elusive; in addition, previous neuroimaging studies about loneliness mainly focused on the elderly and were limited by small sample sizes. Here, utilizing the voxel-based morphometry (VBM) approach via structural magnetic resonance imaging, we investigated the association between brain GMV and loneliness in 462 young adults (67.7% females, age = 18.59 ± 1.14 years). Results from whole-brain VBM analyses revealed that individuals with higher loneliness tended to have greater GMV in the right dorsolateral prefrontal cortex (DLPFC), which was thought to be associated with emotional regulation deficits and executive dysfunction. Importantly, the GMV-based predictive models (a machine-learning method) demonstrated that the correlation between loneliness and GMV in the DLPFC was robust. Further, interpersonal self-support traits (ISS), a Chinese indigenous personality construct and pivotal personality factor for resisting negative life outcomes, mediated the relationship between the GMV in the right DLPFC and loneliness. Taken together, the present study reveals that the GMV in right DLPFC acts as an underlying neurostructural correlate of loneliness in the healthy brain, and further provides a brain-personality-symptom pathway for protection against loneliness in which GMV of DLPFC affects loneliness through ISS traits. Future intervention procedures aiming to decrease loneliness and enhance mental health levels among young adults should be developed through improving interpersonal relationships such as social skills training.

Lentivirus-mediated RNA silencing of c-Met markedly suppresses peritoneal dissemination of gastric cancer in vitro and in vivo.

AIM: To investigate the expression of c-Met in peritoneal free cancer cells isolated from human gastric cancer ascites, and its relationship to peritoneal dissemination of gastric cancer. METHODS: Peritoneal free cancer cells (PFCCs) were isolated from ascites specimens of gastric cancer patients. c-Met expression in PFCCs was detected with immunocytochemistry. In human gastric cancer cell line SGC7901, c-Met expression was detected using RT-PCR and Western blot, and was suppressed with lentivirus-mediated RNAi. The proliferation of SGC7901 cells was measured using MTT assay, and the invasion ability was detected with invasion assay. The adhesion of SGC7901 cells to peritoneum was observed in human peritoneal mesothelial cells (HPMCs) monolayer in vitro and in mice in vivo. RESULTS: PFCCs were isolated from ascites of 6 out of 10 gastric cancer patients. c-Met expression in PFCCs was detected in 5 of the 6 gastric cancer patients. In SGC7901 cells, Lentivirus-mediated RNAi significantly reduced both c-Met mRNA and protein expression, which resulted in suppressing the cell proliferation, invasion and adhesion to peritoneum. The expression of α3ß1 integrin and E-cadherin was significantly inhibited in SGC7901 cells transfected with Lenti-miRNAc-Met. In the peritoneal dissemination model of gastric cancer, intraperitoneal injection of Lenti-miRNAc-Met markedly suppressed the tumor Progression of SGC7901 cells. CONCLUSION: c-Met is expressed in PFCCs from the ascites of gastric cancer patients. Down-regulation of c-Met expression markedly suppresses the multistep process of peritoneal dissemination, thus may be a potential target for the treatment of gastric cancer.