Connectome-based individualized prediction of reciprocity propensity and sensitivity to framing: a resting-state functional magnetic resonance imaging study.

BACKGROUND: The social representation theory states that individual differences in reciprocity decisions are composed of a stable central core (i.e., reciprocity propensity, RP) and a contextual-dependent periphery (i.e., sensitivity to the framing effect; SFE, the effect by how the decision is presented). However, the neural underpinnings that explain RP and SFE are still unknown. METHOD: Here, we employed prediction and lesion models to decode resting-state functional connectivity (RSFC) of RP and SFE for reciprocity decisions of healthy volunteers who underwent RS functional magnetic resonance imaging and completed one-shot trust (give frame) and distrust (take frame) games as trustees. RESULTS: Regarding the central core, reciprocity rates were positively associated between the give and take frame. Neuroimaging results showed that inter-network RSFC between the default-mode network (DMN; associated with mentalizing) and cingulo-opercular network (associated with cognitive control) contributed to the prediction of reciprocity under both frames. Regarding the periphery, behavioral results demonstrated a significant framing effect-people reciprocated more in the give than in the take frame. Our neuroimaging results revealed that intra-network RSFC of DMN (associated with mentalizing) contributed dominantly to the prediction of SFE. CONCLUSION: Our findings provide evidence for distinct neural mechanisms of RP and SFE in reciprocity decisions.

Role of the amygdala in disrupted integration and effective connectivity of cortico-subcortical networks in apathy.

BACKGROUND: Apathy is a quantitative reduction in motivation and goal-directed behaviors, not only observed in neuropsychiatric disorders, but also present in healthy populations. Although brain abnormalities associated with apathy in clinical disorders have been studied, the organization of brain networks in healthy individuals has yet to be identified. METHOD: We examined properties of intrinsic brain networks in healthy individuals with varied levels of apathy. By using functional magnetic resonance imaging in combination with graph theory analysis and dynamic causal modeling analysis, we tested communications among nodes and modules as well as effective connectivity among brain networks. RESULTS: We found that the average participation coefficient of the subcortical network, especially the amygdala, was lower in individuals with high than low apathy. Importantly, we observed weaker effective connectivity fromthe hippocampus and parahippocampal gyrus to the amygdala, and from the amygdala to the parahippocampal gyrus and medial frontal cortex in individuals with apathy. CONCLUSION: These findings suggest that individuals with high apathy exhibit aberrant communication within the cortical-to-subcortical network, characterized by differences in amygdala-related effective connectivity. Our work sheds light on the neural basis of apathy in subclinical populations and may have implications for understanding the development of clinical conditions that feature apathy.

Individualized prediction of consummatory anhedonia from functional connectome in major depressive disorder.

BACKGROUND: Anhedonia is a key symptom of major depressive disorder (MDD) and other psychiatric diseases. The neural basis of anhedonia has been widely examined, yet the interindividual variability in neuroimaging biomarkers underlying individual-specific symptom severity is not well understood. METHODS: To establish an individualized prediction model of anhedonia, we applied connectome-based predictive modeling (CPM) to whole-brain resting-state functional connectivity profiles of MDD patients. RESULTS: The CPM can successfully and reliably predict individual consummatory but not anticipatory anhedonia. The predictive model mainly included salience network (SN), frontoparietal network (FPN), default mode network (DMN), and motor network. Importantly, subsequent computational lesion prediction and consummatory-specific model prediction revealed that connectivity of the SN with DMN and FPN is essential and specific for the prediction of consummatory anhedonia. CONCLUSIONS: This study shows that brain functional connectivity, especially the connectivity of SN-FPN and SN-DMN, can specifically predict individualized consummatory anhedonia in MDD. These findings suggest the potential of functional connectomes for the diagnosis and prognosis of anhedonia in MDD and other disorders.

Single dose testosterone administration enhances novelty responsiveness and short-term habituation in healthy males.

The role of testosterone in sensory perception suggests that testosterone likely regulates adaptive responses to sensory changes, including habituation to repeated events and responsiveness to novel events. To test this hypothesis, we investigated how testosterone modulates brain responses to rapid changes in sensory inputs. Using a double-blind, placebo-controlled, within-participant design, each participant received a single dose of either testosterone or placebo, and then completed a passive auditory oddball task in which infrequent deviant tones were embedded in a series of frequent standard tones. Analysis of novelty-evoked potentials revealed smaller Mismatch Negativity (MMN) responses, but larger P3a responses in the testosterone session than in the placebo session. This suggests testosterone attenuates MMN responses that are associated with pre-attentive novelty detection and enhances P3a responses that are associated with involuntary attentional orientation toward novelty. Along with the repetition of standard tones, P2 responses on the auditory evoked potentials became significantly attenuated in the testosterone session, but not in the placebo session. This suggests testosterone enhances short-term habituation of P2 responses to recurring sensory events, which has been associated with bottom-up attention allocation. Mediation analysis further revealed that the role of testosterone in promoting attentional orientation toward novelty could be explained by the influence it exerts on short-term habituation and pre-attentive novelty detection. Overall, testosterone facilitated involuntary attention switching-withdrawal of attention from repeated sensory events and orientation toward novel sensory events-at the cost of attenuated pre-attentive novelty detection. This finding provides insight into the interplay between endocrinology and involuntary attentional processes.

The anatomical structure of sex differences in trust propensity: A voxel-based morphometry study.

Trust is a key component of human relationships. Sex differences in trust behavior have been elucidated by parental investment theory and social role theory, attributing men's higher trust propensity to their increased engagement in physically and socially risky activities aimed at securing additional resources. Although sex differences in trust behavior exist and the neuropsychological signatures of trust are known, the underlying anatomical structure of sex differences is still unexplored. Our study aimed to investigate the anatomical structure of sex differences in trust behavior toward strangers (i.e., trust propensity, TP) by employing voxel-based morphometry (VBM) in a sample of healthy young adults. We collected behavioral data for TP as measured with participants in the role of trustors completing the one-shot trust game (TG) with anonymous partners as trustees. We conducted primary region of interest (ROI) and exploratory whole-brain (WB) VBM analyses of high-resolution structural images to test for the association between TP and regional gray matter volume (GMV) associated with sex differences. Confirming previous studies, our behavioral results demonstrated that men trusted more than women during the one-shot TG. Our WB analysis showed a greater GMV related to TP in men than women in the precuneus (PreC), whereas our ROI analysis in regions of the default-mode network (dorsomedial prefrontal cortex [dmPFC], PreC, superior temporal gyrus) to simulate the partner's trustworthiness, central-executive network (ventrolateral PFC) to implement a calculus-based trust strategy, and action-perception network (precentral gyrus) to performance cost-benefit calculations, as proposed by a neuropsychoeconomic model of trust. Our findings advance the neuropsychological understanding of sex differences in TP, which has implications for interpersonal partnerships, financial transactions, and societal engagements.

The mechanical mechanism of angiotensin II induced activation of hepatic stellate cells promoting portal hypertension.

In the development of chronic liver disease, the hepatic stellate cell (HSC) plays a pivotal role in increasing intrahepatic vascular resistance (IHVR) and inducing portal hypertension (PH) in cirrhosis. Our research demonstrated that HSC contraction, prompted by angiotensin II (Ang II), significantly contributed to the elevation of type I collagen (COL1A1) expression. This increase was intimately associated with enhanced cell tension and YAP nuclear translocation, mediated through α-smooth muscle actin (α-SMA) expression, microfilaments (MF) polymerization, and stress fibers (SF) assembly. Further investigation revealed that the Rho/ROCK signaling pathway regulated MF polymerization and SF assembly by facilitating the phosphorylation of cofilin and MLC, while Ca2+ chiefly governed SF assembly via MLC. Inhibiting α-SMA-MF-SF assembly changed Ang II-induced cell contraction, YAP nuclear translocation, and COL1A1 expression, findings corroborated in cirrhotic mice models. Overall, our study offers insights into mitigating IHVR and PH through cell mechanics, heralding potential breakthroughs.

Cognitive empathy mediates the relationship between gray matter volume size of dorsomedial prefrontal cortex and social network size: A voxel-based morphometry study.

Social networks are an important factor in developing and maintaining social relationships. The social brain network comprises brain regions that differ in terms of their location, structure, and functioning, and these differences tend to vary among individuals with different social network sizes. However, it remains unknown how social cognitive abilities such as empathy can affect social network size. The goal of our study was to examine the relationship between brain regions in the social brain network, empathy, and individual social network size by using the Social Network Index, which measures social network diversity, size, and complexity by assessing 12 different types of relationships. We performed voxel-based morphometry and mediation analyses using data from questionnaires and structural magnetic resonance imaging data in a sample of 204 young adults. Our findings showed that the gray matter volume of the dorsomedial prefrontal cortex (dmPFC) was inversely associated with social network size and cognitive empathy mediated this association, suggesting that decreased gray matter volume in the dmPFC is associated with greater utilization of cognitive empathy, which, in turn, seems to increase social network size. A potential mechanism explaining this inverse relationship could be cognitive pruning, a phenomenon that occurs in the brain between early adolescence and adulthood, but future longitudinal studies are needed. In conclusion, our findings provide information about the neurocognitive mechanisms involved in the formation and maintenance of social networks.

Performance monitoring moderates the relationship between stress and negative affect in response to an exam stressor.

The present longitudinal study examined the role of performance monitoring in the relationships between stress (both stress change and chronic stress) and negative affect to a real-life stressor-final exam among 60 undergraduates. Participants firstly completed a Go/No-Go task in the laboratory with electroencephalogram recordings. At T1 (31 days before the final exam), participants reported their chronic perceived stress. Then, with the daily dairy method, their daily stress level and negative affect were collected for three consecutive days. At T2 (three days before the final exam), the 3-day daily dairy was repeated. Results showed that performance monitoring, as measured by behavioral adjustments and electrophysiological correlates, moderated the effects of stress change as well as chronic perceived stress on the negative emotional response to the final exam. More specifically, as the stress change from baseline to exam increases, individuals with shorter PES, lower PEAD or larger Pe amplitudes experienced less negative affect increases in response to exam. Additionally, individuals with shorter PES or larger Pe amplitudes showed no significant relationship between chronic stress and negative affect, whereas individuals with longer PES or smaller Pe amplitudes showed significant positive relationship between chronic stress and negative affect increases in response to exam. The results demonstrated that efficient performance monitoring is a protective factor for stress.

Effects of lactate on metabolism and differentiation of CD4+T cells.

BACKGROUND: Lactate accumulation caused by abnormal tumor metabolism can induce the formation of an inhibitory immune microenvironment through a variety of pathways, which is characterized by regulatory T cells (Treg) infiltration and effector T cells (Teff) depletion. Studies have found that the key reason why Treg cells can survive in harsh environments lies in their flexible metabolic mode, which can use lactate in tumor microenvironment (TME) as an alternative energy substance to maintain their inhibitory activity. In addition, lactate could also promote the differentiation of CD4+T cells into Treg, but the mechanism was not completely clear. The purpose of this study was to investigate the possible mechanism by which lactate is utilized by CD4+T cells to influence Th17/Treg ratio. METHODS: Basal cytokines (anti-CD3, anti-CD28, TGF-ß) and 10 mM lactate was added into Naïve CD4+T cells basal medium for 3 days. After TCR stimulation, Naïve CD4+T converted to CD4+T. Flow cytometry was used to detect the proportion of Treg cells; ELISA was used to detect the activity of LDHA, LDHB and NADH and the amount of α -Ketoglutaric Acid (α-KG) and 2-Hydroxyglutaric Acid (2HG) after lactate entered the cells; Western Blot and RT-PCR were used to detect the protein and gene expression of Foxp3, RORγt, LDHA and LDHB. In the validation experiment, lactate uptake inhibitor AZD3965, LDHA inhibitor GSK2837808A and NADH conversion inhibitor Rotenone were added respectively to observe the differentiation ratio of Treg cells and confirm the key points of metabolism; the degradation of Treg cell transcription factor Foxp3 was interfered with ubiquitination inhibitors to observe whether it co-ubiquitinated with HIF-1α; the expression and activity of LDHA, LDHB and NADH in mitochondria and cytoplasm were detected to confirm cell localization. RESULTS: When basal cytokines (anti-CD3, anti-CD28, TGF-ß) stimulated, lactate was added to the culture medium, and CD4+T cells absorbed a large amount of lactate not only through MCT1 (monocarboxylic acid transporter), but also increased the expression of lactate dehydrogenase and accelerated the intracellular metabolism of lactate. LDHB in cytoplasm mainly catalyzed the dehydrogenation of lactate to pyruvate, accompanied by the transformation reaction between NAD+ and NADH. The latter further entered the mitochondria and participates in the tricarboxylic acid cycle metabolism. In addition, lactate could significantly increase the level of LDHA in mitochondria and promote the transformation of α-KG to 2HG, accompanied by the transformation of NADH to NAD+. These metabolic changes eventually led to an increase in the intracellular 2HG/α-KG ratio. Abnormal 2HG increased the proportion of Treg by inhibiting ATP5B-mediated phosphorylation of mTOR and the synthesis of HIF-1α, causing it not be enough to ubiquitinate and degrade with Foxp3. CONCLUSIONS: Lactate plays an important role in regulating the differentiation of Treg cells, inducing the expression and function of LDHA and promoting the transformation of α-KG to 2HG may be an important mechanism.

Neurocognitive correlates of psychological resilience: Event-related potential studies.

BACKGROUND: There is a growing interest in exploring the neurocognitive mechanisms that may underlie psychological resilience. However, how the bottom-up automatic information processing relates to trait resilience has received less attention. We aimed to explore the relationship between trait resilience and trait-like automatic information processing in healthy adults. METHODS: Eighty-four healthy adults were recruited to explore whether and how resilience was related to sensory sensitivity by event-related potentials (ERPs). Resilience was measured by Connor-Davidson Resilience Scale (CD-RISC). Sensory sensitivity, more specifically, sensitivity of automatic mismatch detection was measured by two ERPs components, i.e., the mismatch negativity (MMN) with a passive auditory oddball paradigm and the error-related negativity (ERN) with an auditory Go/NoGo task. Using the multiple linear regression analyses, the relationship between self-reported resilience and the sensitivity of automatic mismatch detection (MMN/ERN amplitude/latency) was explored. RESULTS: The results showed that psychological resilience was positively correlated with both MMN and ERN latencies, i.e., higher resilience scores were associated with delayed MMN and ERN latencies. However, resilience was not significantly correlated with MMN and ERN amplitudes. CONCLUSIONS: Our results suggested that relatively higher resilience might link with less sensory sensitivity as reflected by slower automatic detection to mismatch information in the environment.

Midkine mediates dysfunction of liver sinusoidal endothelial cells through integrin α4 and α6.

Midkine (MK)2 is an important regulatory molecule that promotes pathological angiogenesis of hepatocellular carcinoma (HCC). Although some studies have shown that its expression is increased in chronic liver disease, its effect on sinusoidal vasculopathy are still unclear. In this study, we demonstrated that MK was mainly secreted by liver sinus endothelial cells (LSECs) during the stage of precancerous lesions. Increased expression of its receptor integrin was an important mechanism by which MK participated in sinusoidal vasculopathy through autocrine and positive feedback effects. LSECs with high expression of integrin α6 (Itgα6+) and integrin α4 (Itgα4+) were used to study the mechanism of MK, and it was found that the effect of MK on LSECs was closely related to the integrin subtypes. The activation of MK /integrin α6/Src/Shc signaling pathway promoted the expression of ET-1, TXA2 and reduced the production of NO, and then induced the capillary vascularization of liver sinusoids, while the activation of MK/integrin α4/NF-κB pathway mainly induced angiogenesis by promoting the production of VEGF and Ang2. In the three-dimensional co-culture system of hepatocytes (BRL-3A) and LSECs, MK significantly increased the production of reactive oxygen species (ROS) in the co-culture system of highly expressed integrin LSECs and decreased the expression of tumor suppressor gene P53 in hepatocytes. These results suggested that MK /integrin signaling pathway, especially MK /integrin α6, was an important mechanism leaded to persistent sinusoidal hepatic vasculopathy in chronic liver disease and induced HCC，while MK/integrin α 4 activation was more involved in pathological angiogenesis.

The relationship between childhood stress and distinct stages of dynamic behavior monitoring in adults: neural and behavioral correlates.

Childhood adversity is a major risk factor for emotional and cognitive disorders later in adulthood. Behavior monitoring, one of the most important components of cognitive control, plays a crucial role in flexible interaction with the environment. Here, we test a novel conceptual model discriminating between two distinct dimensions of childhood adversity (i.e. deprivation and threat) and examine their relations to dynamic stages of behavior monitoring. Sixty young healthy adults participated in this study using event-related potentials and the dynamic stages of behavior monitoring including response inhibition, error detection and post-error adjustments were investigated in a classical Go/NoGo task. Multiple regression analyses revealed that participants with higher severity of childhood adversity recruited more controlled attention, as indicated by larger (more negative) conflict detection-related NoGo-N2 amplitudes and larger (more negative) error detection-related error-related negativity amplitudes. Higher severity of childhood abuse (an indicator of threat) was related to smaller (less positive) error appraisal-related error positivity amplitudes on the neural level and subsequently lower post-error accuracy on the behavioral level. These results suggested that prefrontal-supported controlled attention is influenced by universal adversity in childhood while the error-related behavioral adjustment is mainly affected by childhood abuse, indicating the dimensions of deprivation and threat are at least partially distinct.

Single dose testosterone administration modulates the temporal dynamics of distractor processing.

Some evidence suggests that testosterone can increase attentional orientation toward biologically relevant stimuli and increase sustained attention during goal-oriented behaviors. While rare irregular distractors often capture attention involuntarily and distract us away from the task at hand, we hypothesized that testosterone might (1) facilitate attentional orientation to novel distractors that are of potential behavioral relevance and (2) inhibit information processing of distractors that are irrelevant to the task. To test this hypothesis, we investigated the effects of testosterone on distractor processing in a novelty oddball task, during which infrequent target and distractor sounds were interspersed within a series of frequent non-target sounds. Using a double-blind, placebo-controlled within-participant design, we administered a single dose of either testosterone or placebo to 34 healthy male volunteers and compared their electroencephalographic responses to distractors. Increased amplitude of the early (260-310 ms) P3 component-which has been associated with phasic arousal and alertness triggered by novel stimuli-was observed in the testosterone session than in the placebo session. This early-P3 response mediated the effect of testosterone administration on target hit rate during the task. In addition, less α-oscillation suppression-which has been associated with the inhibition of task-irrelevant information processing-was observed in response to distractors later (538-757 ms) in the testosterone session than in the placebo session. These results suggest that testosterone facilitated phasic arousal to novel distractors during the early-latency stage, which might have influenced behavioral performance during the task. Furthermore, testosterone inhibited task-irrelevant information processing during the late-latency stage, which allowed better reorientation of attention back to the primary task. Our findings highlight the role of testosterone in distractor processing, and provide a theoretical basis for treating attention-related behavioral disorders with hormone therapies.

The relationship between chronic perceived stress and error processing: evidence from event-related potentials.

Prolonged exposure to stress has a wide effect on the brain and cognition. Error processing, as one of the crucial components of executive function, plays an important role in cognitive and behavior control. However, to date, there is little research addressing the relationship between chronic perceived stress and error processing. The present study aims to explore the relationship between chronic perceived stress by the Cohen Perceived Stress Scale (PSS) and different stages of error processing by the method of Event-Related Potential (ERP). The error processing was tested in a classical auditory Go/NoGo paradigm, and ERP components including early Error-related Negativity (ERN) and late Error Positivity (Pe) were computed as the indices of error processing. The results showed that the PSS score was positively correlated with the Pe amplitude but not with the ERN amplitude. The correlation between PSS and the Pe amplitude holds true even after controlling the trait anxiety and depression symptoms. These results suggest that the higher the chronic stress level, the more sensitive the individuals are to their own errors as well as the more emotional/motivated attention the individuals distributed to their own errors.

Associations between cortisol awakening response and resting electroencephalograph asymmetry.

The cortisol awakening response (CAR), a rapid cortisol rise in the morning after awakening, has been proposed to provide energy to cope with daily demands and suggested to be associated with brain functions. Electroencephalogram (EEG) asymmetry studies have implicated asymmetric cortical activation, especially in frontal cortex, in approach-withdrawal motivation. In this study, we examined the relationship between the CAR and lateralized cortical activity under rest in 55 university male students. Saliva samples were collected at 0, 15, 30 and 60 min after awakening on the two consecutive workdays. The lateralized cortical activity at frontocentral sites was examined by alpha asymmetry score. The results showed that a higher CAR was positively associated with alpha asymmetry score, which indicated that the higher CAR is linked with more left-sided cortical activity at frontocentral sites under resting state. This association still existed even after controlling psychological and sleep quality variables. These results suggested that appropriately mobilizing energy resource storage after awakening revealed as CAR might be associated with goal-directed approach tendencies before any eventual stressful situation, characteristic of more left than right resting-state frontocentral cortical activity.