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Abstract Face perception is a fundamental aspect of human social interaction, yet most research on this topic has focused on single modalities and specific aspects of face perception. Here, we present a comprehensive multimodal dataset for examining facial emotion perception and judgment. This dataset includes EEG data from 97 unique neurotypical participants across 8 experiments, fMRI data from 19 neurotypical participants, single-neuron data from 16 neurosurgical patients (22 sessions), eye tracking data from 24 neurotypical participants, behavioral and eye tracking data from 18 participants with ASD and 15 matched controls, and behavioral data from 3 rare patients with focal bilateral amygdala lesions. Notably, participants from all modalities performed the same task. Overall, this multimodal dataset provides a comprehensive exploration of facial emotion perception, emphasizing the importance of integrating multiple modalities to gain a holistic understanding of this complex cognitive process. This dataset serves as a key missing link between human neuroimaging and neurophysiology literature, and facilitates the study of neuropsychiatric populations.

Abstract Processing facial expressions of emotion draws on a distributed brain network. In particular, judging ambiguous facial emotions involves coordination between multiple brain areas. Here, we applied multimodal functional connectivity analysis to achieve network-level understanding of the neural mechanisms underlying perceptual ambiguity in facial expressions. We found directional effective connectivity between the amygdala, dorsomedial prefrontal cortex (dmPFC), and ventromedial PFC, supporting both bottom-up affective processes for ambiguity representation/perception and top-down cognitive processes for ambiguity resolution/decision. Direct recordings from the human neurosurgical patients showed that the responses of amygdala and dmPFC neurons were modulated by the level of emotion ambiguity, and amygdala neurons responded earlier than dmPFC neurons, reflecting the bottom-up process for ambiguity processing. We further found parietal-frontal coherence and delta-alpha cross-frequency coupling involved in encoding emotion ambiguity. We replicated the EEG coherence result using independent experiments and further showed modulation of the coherence. EEG source connectivity revealed that the dmPFC top-down regulated the activities in other brain regions. Lastly, we showed altered behavioral responses in neuropsychiatric patients who may have dysfunctions in amygdala-PFC functional connectivity. Together, using multimodal experimental and analytical approaches, we have delineated a neural network that underlies processing of emotion ambiguity.

Abstract People judge the nature of human behaviors based on underlying intentions and possible outcomes. Recent studies have demonstrated a causal role of the right temporoparietal junction (rTPJ) in modulating both intention and intention-based outcome evaluations during social judgments. However, these studies mainly used hypothetical scenarios with socially undesirable contexts (bad/neutral intentions and bad/neutral outcomes), leaving the role of rTPJ in judging good intentions and good outcomes unclear. In the current study, participants were instructed to make goodness judgments as a third party toward the monetary allocations from one proposer to another responder. Critically, in some cases, the initial allocation by the proposer could be reversed by the computer, yielding combinations of good/bad intentions (of the proposer) with good/bad outcomes (for the responder). Anodal (n = 20), cathodal (n = 21), and sham (n = 21) transcranial direct current stimulation (tDCS) over the rTPJ were randomly assigned to 62 subjects to further examine the effects of stimulation over the rTPJ in modulating intention-based outcome evaluation. Compared to the anodal and sham stimulations, cathodal tDCS over the rTPJ reduced the goodness ratings of good/bad outcomes when the intentions were good, whereas it showed no significant effect on outcome ratings under unknown and bad intentions. Our results provide the first evidence that deactivating the rTPJ modulates outcome evaluation in an intention-dependent fashion, mainly by reducing the goodness rating towards both good/bad outcomes when the intentions are good. Our findings argue for a causal role of the rTPJ in modulating intention-based social judgments and point to nuanced effects of rTPJ modulation.

Abstract Patients undergoing unilateral orthopedic or neurological rehabilitation have different levels of impairments in the right- or left-dominant hand. However, how handedness and the complexity of the motor task affect motor skill acquisition and its interlimb transfer remains unknown. In the present study, participants performed finger key presses on a numeric keypad at 4 levels of sequence complexities with each hand in a randomized order. Furthermore, they also performed motor sequence practice with the dominant hand to determine its effect on accuracy, reaction time, and movement time. The NASA-TLX at the end of each block of both testing and practice was used to confirm participants’ mental workload related to sequence complexity. Both right- and left-handed participants performed the motor sequence task with faster RT when using their right hand. Although participants had increasing RT with increasing sequence complexity, this association was unrelated to handedness. Motor sequence practice produced motor skill acquisition and interlimb transfer indicated by a decreased RT, however, these changes were independent of handedness. Higher sequence complexity was still associated with longer RT after the practice, moreover, both right- and left-handed participants’ RT increased with the same magnitude with the increase in sequence complexity. Similar behavioral pattern was observed in MT as in RT. Overall, our RT results may indicate left-hemisphere specialization for motor sequencing tasks, however, neuroimaging studies are needed to support these findings. On the other hand, handedness did not affect motor skill acquisition by the dominant hand or interlimb transfer to the non-dominant hand regardless of task complexity level.

Humans adjust their behavioral strategies based on feedback, a process that may depend on intrinsic preferences and contextual factors such as visual salience. In this study, we hypothesized that decision-making based on visual salience is influenced by habitual and goal-directed processes, which can be evidenced by changes in attention and subjective valuation systems. To test this hypothesis, we conducted a series of studies to investigate the behavioral and neural mechanisms underlying visual salience-driven decision-making. We first established the baseline behavioral strategy without salience in Experiment 1 (n = 21). We then highlighted the utility or performance dimension of the chosen outcome using colors in Experiment 2 (n = 30). We demonstrated that the difference in staying frequency increased along the salient dimension, confirming a salience effect. Furthermore, the salience effect was abolished when directional information was removed in Experiment 3 (n = 28), suggesting that the salience effect is feedback-specific. To generalize our findings, we replicated the feedback-specific salience effects using eye-tracking and text emphasis. The fixation differences between the chosen and unchosen values were enhanced along the feedback-specific salient dimension in Experiment 4 (n = 48) but unchanged after removing feedback-specific information in Experiment 5 (n = 32). Moreover, the staying frequency was correlated with fixation properties, confirming that salience guides attention deployment. Lastly, our neuroimaging study (Experiment 6, n = 25) showed that the striatum subregions encoded salience-based outcome evaluation, while the vmPFC encoded salience-based behavioral adjustments. The connectivity of the vmPFC-ventral striatum accounted for individual differences in utility-driven, whereas the vmPFC-dmPFC for performance-driven behavioral adjustments. Together, our results provide a neurocognitive account of how task-irrelevant visual salience drives decision-making by involving attention and the frontal-striatal valuation systems. Public significance statement: Humans may use the current outcome to make behavior adjustments. How this occurs may depend on stable individual preferences and contextual factors, such as visual salience. Under the hypothesis that visual salience determines attention and subsequently modulates subjective valuation, we investigated the underlying behavioral and neural bases of visual-context-guided outcome evaluation and behavioral adjustments. Our findings suggest that the reward system is orchestrated by visual context and highlight the critical role of attention and the frontal-striatal neural circuit in visual-context-guided decision-making that may involve habitual and goal-directed processes.

With the rapid growth of Transportation Network Company (TNC) services and the continued decline of transit ridership, existing research has proposed and some transit agencies have implemented programs that integrate transit and TNC services. This paper expands the research area to examine the equity implications of such integrations, focusing on job accessibility improvements for low-income workers. We develop an analytical framework that compares improvements in accessibility to jobs under different hypothetical scenarios in which TNC travel serves as the last-mile connection of transit services. Using the city of Chicago for the case study, this research confirms that such transit-TNC integration increases job accessibility for all low-income workers throughout the city, but it also pinpoints nuanced differences in the accessibility improvements among workers of different races, ethnicities, and sexes during peak and off-peak hours.

When faced with uncertainty, individuals’ value-based decisions are influenced by the expected rewards and risks. Understanding how reward and risk are processed and integrated at the behavioral and neural levels is essential for building up utility theories. Using a modified monetary incentive delay task in which the mean of two possible outcomes (expected reward) and the standard deviation (SD) of the possible outcomes (risk) were parametrically manipulated and orthogonalized, we measured eye movements, response times (RTs), and brain activity when participants seek to secure a reward. We found that RTs varied as a function of the mean but not the SD of the potential reward, suggesting that expected rewards are the main driver of RTs. Moreover, the difference between gazes focused on high vs. low value rewards became smaller when the magnitude of the potential reward (mean of possible outcomes) was larger and when risk (SD of possible outcomes) became smaller, highlighting that reward and risk have different effects on attention deployment. Processing the mean reward activated the striatum. The positive striatal connectivity to the amygdala and negative striatal connectivity to the superior frontal gyrus were correlated with individuals’ sensitivity to the expected reward. In contrast, processing risk activated the anterior insula. Its positive connectivity to the ventromedial prefrontal cortex and negative connectivity to the anterior midcingulate cortex were correlated with individual differences in risk sensitivity, further suggesting the functional dissociation of reward and risk at the neural level. Our findings, based on several different measures, delineate the distinct representations of reward and risk in non-decision contexts and provide insight into how these utility parameters modulate attention, motivation, and brain networks.

Human decision-making can be influenced by whether the option is framed as positive or negative, known as the framing effect. Neuroeconomic studies have shown the engagement of the amygdala underlies the framing effect by automatically incorporating emotional (or intuitive) information into the decision process, thus leading to ''irrational'' decisions or decision biases (De Martino et al. 2006). However, these studies focus only on the gain domain in which the initial state is appetitive, leaving the mechanisms of the framing effect in the loss or aversive domain less understood, which could be equally important or even more dominant for human survival. In the present study, we first replicated De Martino et al.’s research on the framing effect in the gain domain. We then checked the commonality and distinctiveness of the framing effect across gain and loss domains using a similar experimental design combined with functional magnetic resonance imaging (fMRI). Behaviorally, participants showed comparable framing effects in both domains, suggesting a domain-general decision bias. Neuronally, the amygdala represented the framing effect for the gain domain, and its connectivity to vmPFC was positively modulated by framing bias, consistently shown in De Martino et al.’s study. Moreover, the striatum represented the framing effect for the loss domain, and its connectivity to dmPFC was subject to framing bias, suggesting distinctive neural substrates across two domains. Our study accentuates the importance of distinguishing decision processes across appetitive or aversive domains and highlights the role of the cortical-striatal-limbic network underlying the framing effect.

Reduced graphene oxide (RGO) has been extensively studied and applied in optoelectronic systems, but its unstable dispersion in organic solvents has limited its application. To overcome this problem, the newly designed and developed aggregation-induced emission (AIE) material poly[(9,9-bis(6-azidohexyl)-9H-fluorene)-alt-(9-(4-(1,2,2-triphenylvinyl)phenyl)-9H-carbazole)] (PAFTC) was covalently grafted onto RGO to produce (PFTC-g-RGO). The solubility of two-dimensional graphene was improved by incorporating it into the backbone of PAFTC to form new functional materials. In resistive random access memory (RRAM) devices, PFTC-g-RGO was used as the active layer material after it was characterized. The fabricated Al/PFTC-g-RGO/ITO device exhibited nonvolatile bistable resistive switching performances with a long retention time of over 104 s, excellent endurance of over 200 switching cycles, and an impressively low turn-ON voltage. This study provides important insights into the future development of AIE polymer-functionalized nanomaterials for information storage.

Risk and ambiguity are inherent in virtually all human decision-making. Risk refers to a situation in which we know the precise probability of potential outcomes of each option, whereas ambiguity refers to a situation in which outcome probabilities are not known. A large body of research has shown that individuals prefer known risks to ambiguity, a phenomenon known as ambiguity aversion. One heated debate concerns whether risky and ambiguous decisions rely on the same or distinct neural circuits. In the current meta-analyses, we integrated the results of neuroimaging research on decision-making under risk (n = 69) and ambiguity (n = 31). Our results showed that both processing of risk and ambiguity showed convergence in anterior insula, indicating a key role of anterior insula in encoding uncertainty. Risk additionally engaged dorsomedial prefrontal cortex (dmPFC) and ventral striatum, whereas ambiguity specifically recruited the dorsolateral prefrontal cortex (dlPFC), inferior parietal lobe (IPL) and right anterior insula. Our findings demonstrate overlapping and distinct neural substrates underlying different types of uncertainty, guiding future neuroimaging research on risk-taking and ambiguity aversion.

People often make decisions in the face of ambiguous information, but it remains unclear how ambiguity is represented in the brain. We used three types of ambiguous stimuli and combined EEG and fMRI to examine the neural representation of perceptual decisions under ambiguity. We identified a late positive potential, the LPP, which differentiated levels of ambiguity, and which was specifically associated with behavioral judgments about choices that were ambiguous, rather than passive perception of ambiguous stimuli. Mediation analyses together with two further control experiments confirmed that the LPP was generated only when decisions are made (not during mere perception of ambiguous stimuli), and only when those decisions involved choices on a dimension that is ambiguous. A further control experiment showed that a stronger LPP arose in the presence of ambiguous stimuli compared to when only unambiguous stimuli were present. Source modeling suggested that the LPP originated from multiple loci in cingulate cortex, a finding we further confirmed using fMRI and fMRI-guided ERP source prediction. Taken together, our findings argue for a role of an LPP originating from cingulate cortex in encoding decisions based on task-relevant perceptual ambiguity, a process that may in turn influence confidence judgment, response conflict, and error correction.

The amygdala processes emotional facial expressions, but its exact contributions are unclear. Wang.et al. use behavioural analysis of amygdala lesion patients, fMRI, and single-neuron recordings to show that both emotional intensity and ambiguity signals are processed in the human amygdala.

When people have different opinions in a group, they often adjust their own attitudes and behaviors to match the group opinion, known as social conformity. The affiliation account of normative conformity states that people conform to norms in order to 'fit in', whereas the accuracy account of informative conformity posits that the motive to learn from others produces herding. Here, we test another possibility that following the crowd reduces the experienced negative emotion when the group decision turns out to be a bad one. Using event related potential (ERP) combined with a novel group gambling task, we found that participants were more likely to choose the option that was predominately chosen by other players in previous trials, although there was little explicit normative pressure at the decision stage and group choices were not informative. When individuals' choices were different from others, the feedback related negativity (FRN), an ERP component sensitive to losses and errors, was enhanced, suggesting that being independent is aversive. At the outcome stage, the losses minus wins FRN effect was significantly reduced following conformity choices than following independent choices. Analyses of the P300 revealed similar patterns both in the response and outcome period. Our study suggests that social conformity serves as an emotional buffer that protects individuals from experiencing strong negative emotion when the outcomes are bad.

Abstract The continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the recently circulating Omicron sub-lineages BA.2.86 and JN.1. Here, we report the isolation of broad and potent neutralizing human mAbs (HuMabs) from a healthcare worker infected with SARS-CoV-2 early in the pandemic. These include a genetically unique HuMab, named K501SP6, which can neutralize different Omicron sub-lineages, including BQ.1, XBB.1, BA.2.86 and JN.1, by targeting a highly conserved epitope on the N terminal domain, as well as an RBD-specific HuMab (K501SP3) with high potency towards earlier circulating variants that was escaped by the more recent Omicron sub-lineages through spike F486 and E484 substitutions. Characterizing SARS-CoV-2 spike-specific HuMabs, including broadly reactive non-RBD-specific HuMabs, can give insight into the immune mechanisms involved in neutralization and immune evasion, which can be a valuable addition to already existing SARS-CoV-2 therapies.

Abstract Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.

Pyrimidine nucleotide biosynthesis is a druggable metabolic dependency of cancer cells, and chemotherapy agents targeting pyrimidine metabolism are the backbone of treatment for many cancers. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine biosynthesis pathway that can be targeted by clinically approved inhibitors. However, despite robust preclinical anticancer efficacy, DHODH inhibitors have shown limited single-agent activity in phase 1 and 2 clinical trials. Therefore, novel combination therapy strategies are necessary to realize the potential of these drugs. To search for therapeutic vulnerabilities induced by DHODH inhibition, we examined gene expression changes in cancer cells treated with the potent and selective DHODH inhibitor brequinar (BQ). This revealed that BQ treatment causes upregulation of antigen presentation pathway genes and cell surface MHC class I expression. Mechanistic studies showed that this effect is (1) strictly dependent on pyrimidine nucleotide depletion, (2) independent of canonical antigen presentation pathway transcriptional regulators, and (3) mediated by RNA polymerase II elongation control by positive transcription elongation factor B (P-TEFb). Furthermore, BQ showed impressive single-agent efficacy in the immunocompetent B16F10 melanoma model, and combination treatment with BQ and dual immune checkpoint blockade (anti-CTLA-4 plus anti-PD-1) significantly prolonged mouse survival compared to either therapy alone. Our results have important implications for the clinical development of DHODH inhibitors and provide a rationale for combination therapy with BQ and immune checkpoint blockade.

The new devastating pandemic coronavirus disease 2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome (SARS-CoV-2) has been related to approximately 600 million cases and more than six million deaths till now. After recovery from COVID-19, some patients develop long-term sequelae called long COVID (LC). LC cases have been reported with multi-system involvement, with the most common being neuro-psychiatric, cardiorespiratory, hematological, and gastrointestinal systems highlighting the need for multidisciplinary team involvement and treatment. Since we are more than two and half years into this pandemic, we have more understanding of the pathophysiology and successful treatment of acute COVID-19, and we see more survivors and, subsequently, individuals with LC. However, the pathogenic mechanisms leading to LC are not clear till now. This review describes the potential pathogenic mechanisms leading to LC and common clinical manifestations reported from current evidence.

Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Immunity to placental malaria is acquired through exposure and mediated through antibodies to VAR2CSA. Through evolution, the VAR2CSA proteins have diversified in sequence to escape immune recognition but retained their overall macromolecular structure to maintain CS binding affinity. This structural conservation may also have allowed development of broadly reactive antibodies to VAR2CSA in immune women. Here we show the negative stain and cryo-EM structure of the only known broadly reactive human monoclonal antibody, PAM1.4, in complex with VAR2CSA. The data shows how PAM1.4's broad VAR2CSA reactivity is achieved through interactions with multiple conserved residues of different sub-domains forming conformational epitope distant from the CS binding site on the VAR2CSA core structure. Thus, while PAM1.4 may represent a class of antibodies mediating placental malaria immunity by inducing phagocytosis or NK cell-mediated cytotoxicity, it is likely that broadly CS binding-inhibitory antibodies target other epitopes at the CS binding site. Insights on both types of broadly reactive monoclonal antibodies may aid the development of a vaccine against placental malaria.

Radiotherapy is commonly used in prostate cancer treatment. MnTE-2-PyP is a superoxide dismutase (SOD) mimic that can protect normal tissues from radiation toxicities while simultaneously promoting radiation-induced damage to cancer tissues. Previous work from our laboratory demonstrated that MnTE-2-PyP increased cellular H2O2 levels and led to protein oxidation and DNA damage in prostate cancer cells, which partially contributes to prostate cancer growth arrest. However, the central mechanisms by which MnTE-2-PyP reduces prostate cancer growth remain unclear. In this study, we identified that MnTE-2-PyP depleted cellular reductant levels, especially NADPH, in prostate cancer cells. Correspondingly, we observed a significant decrease in activity of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), which are major cellular NADPH producing enzymes in the pentose phosphate pathway. A decrease of GSH/GSSG ratios were confirmed in MnTE-2-PyP-treated prostate cancer cells, which may result from the decreased glutathione reductase (GR) activity due to NADPH depletion. We also identified that MnTE-2-PyP with radiation significantly increased lipid peroxidation in prostate cancer cells and upregulated sphingomyelin synthesis, which could further consume available NADPH. Thus, MnTE-2-PyP treatment causes lower NADPH levels, resulting in more oxidative stress and membrane damage of prostate cancer cells.

Enterococcus faecium has become an important drug-resistant nosocomial pathogen because of widespread antibiotic abuse. We developed short and chemically simple antimicrobial peptides (AMPs) with a selective amino acid composition, fixed charge, and hydrophobicity ratio based on the core antimicrobial motif of bovine lactoferrin (LfcinB6). Among these peptides, 5L and 6L (both 12 residues long) demonstrated a narrow spectrum and high antibacterial activity against drug-resistant E. faecium isolates with a minimal inhibitory concentration (MIC) that ranged from 4–16 µg/mL. At 32 µg/mL, peptides 5L and 6L inhibited E. faecium strain C68 biofilm formation by 90% and disrupted established biofilms by 75%. At 40 µg/mL, 5L reduced 1 × 107E. faecium persister cells by 3 logs within 120 min of exposure, whereas 6L eliminated all persister cells within 60 min. At 0.5× MIC, 5L and 6L significantly downregulated the expression of a crucial biofilm gene ace by 8 folds (p = 0.02) and 4 folds (p = 0.01), respectively. At 32 µg/mL, peptides 5L and 6L both depolarized the E. faecium membrane, increased fluidity, and eventually ruptured the membrane. Physiologically, 5L (at 8 µg/mL) altered the tricarboxylic acid cycle, glutathione, and purine metabolism. Interestingly, in an ex vivo model of porcine skin infection, compared to no treatment, 5L (at 10× MIC) effectively eliminated all 1 × 106 exponential (p = 0.0045) and persister E. faecium cells (p = 0.0002). In conclusion, the study outlines a roadmap for developing narrow-spectrum selective AMPs and presents peptide 5L as a potential therapeutic candidate to be explored against E. faecium.

In this study, Hawthorn oligomic procyanidins extracts (HPOE) were evaluated for their anticancer activity on colorectal cancer. Our results showed that HPOE arrested HCT116 cells cycle at G2/M phase through P53-Cyclin B pathway and promoted apoptosis partly via mitochondrial (Caspase 9-Caspase 3) and death receptor (Caspase 8-Caspase 3) pathways. Meanwhile, it was found that HPOE aggravated HCT116 cells death through lysosomal vacuolation, which was verified by inhibitor/activator of P53-ILC3 signaling pathway. Taken together, HPOE exerted anticancer effects which lays the foundation for the development of functional foods for clinical colon cancer patients.

Objective To explore the effect of over-expression of triggering receptor on dementia model after traumatic brain injury (TBI) in rat model and potential mechanism. Methods Rats were randomly divided into control group and TBI test groups of 2, 5, 7, 14 and 28 days (n=8). RT-qPCR and Western blot were used to detect trem2 mRNA and protein levels in brain tissues. The remaining 32 rats were randomly divided into 4 groups (n=8): control group, TBI group, (TBI+Null) group and (TBI+ TREM2) group. The (TBI+Null) group was injected with control lentiviral vector, and the (TBI+TREM2) group was injected with the same amount of lentiviral vector encoding TREM2. The memory function of rats in each group was assessed by Morris water maze, and the expression of microglia phenotypes (iNOS and Arg-1), neuroinflammatory related factors(IL-1β, IL-6, IL-4 and IL-10) and cognition-related proteins [amyloid β1-42 (Aβ1-42) and tau] in brain tissues of rats from each group were assessed by RT-qPCR and Western blot. Results Compared with the control group, the expressions of TREM2, TREM2 mRNA, mean escape latency, iNOS, IL-1β, IL-6, Aβ1-42 and Tau were all increased in TBI group, while the expression of Arg-1, IL-4 and IL-10 significantly decreased (P＜0.05). (TBI+TREM2) group significantly alleviated the mean escape latency, increased expression of iNOS, IL-1β, IL-6, Aβ1-42 and Tau, and decreased expression of Arg-1, IL-4 and IL-10 (P＜0.05). Conclusions TREM2 over-expression can regulate the microglial phenotype in brain tissue of TBI rats, reduce the expression of cognition-related proteins (Aβ1-42, tau), and improve the learning and memory function of the animal model.