This study explores the cognitive and neural mechanisms underlying math avoidance in individuals with high math anxiety (HMA), a pattern contributing to reduced practice and poor performance. Using an approach-avoid conflict paradigm and both general linear mixed model and Hierarchical Drift Diffusion Model (HDDM) regression analyses, we found their avoidance behavior is primarily driven by heightened sensitivity to task difficulty, rather than reward sensitivity. Task difficulty sensitivity also mediated the link between math anxiety and avoidance tendency. Neuroimaging revealed distinct activation in the ventral valuation network (e.g., nucleus accumbens, hippocampus) and cognitive control regions (e.g., precuneus, mid-cingulate cortex, temporo-parietal junction) in HMA individuals. Functional connectivity among these regions effectively distinguished HMA from low math anxiety participants. Additionally, activations in the hippocampus, mid-cingulate cortex, and posterior insula mediated the relationship between math anxiety and avoidance. These findings highlight the cognitive and neural bases of math avoidance and may inform targeted interventions.

ObjectivesMyotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism.MethodsWe used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1.ResultsTwenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2.ConclusionThose results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2.

ObjectivesThe presence of dural sinus septum has long been identified anatomically but is often neglected for its clinical significance. Our findings revealed the association of dural sinus septum with venous sinus stenting failure and complications supported by clinical evidence. MethodsThis retrospective study included 185 consecutive patients treated with cerebral venous sinus stenting from January 2009 to May 2022. We identified the dural sinus septa using digital subtraction angiography (DSA) and classified them into three types based on their location. The septa at the transverse sinus were defined as type I, those at the junction between the transverse sinus and sigmoid sinus were defined as type II and those at the sigmoid sinus were defined as type III. Based on the anatomic features and neuroimaging clues, we investigated the correlation of dural sinus septa with stenting failure and complications. Results32 (17.1%) out of 185 patients (121 with idiopathic intracranial hypertension and 64 with venous pulsatile tinnitus) were identified with dural sinus septa by DSA. More than half of the septa were type I (18/32, 56.2%), followed by type II (11/32, 34.4%) and type III (3/32, 9.4%). The dural sinus septa caused three stenting failures and complications, including one case of venous sinus injury with subdural haemorrhage and two cases of incomplete stent expansion. Statistical analysis revealed that the presence of dural sinus septum (p<0.01) was associated with complications of cerebral venous sinus stenting. DiscussionThe dural sinus septum is a common structure in the cerebral venous sinus. We found that the presence of dural sinus septa introduces uncertainties to cerebral venous sinus stenting and suggested precautions and ingenious skills in imaging and treatment.

This study explores how third-party judges weigh the importance of prosociality and fairness when making judgments on complex moral decisions that encompass both elements, and the role of social distance between the judge and the decision-maker in this process. In the experiments, participants acted as third-party observers, watching decisions made by decision-makers in complex moral tasks and evaluating their moral levels. The tasks completed by the decision-makers involved distributing tokens between themselves and others (prosociality) and allocating tokens given to others between two recipients (fairness). The results showed that: 1) the effects of prosociality and fairness on moral judgments are not independent but interactive. Under high prosocial conditions, the difference in moral ratings between fair and unfair decisions is significantly greater than that under low prosocial conditions; at the neural level, the amplitudes of EEG components FRN and P3 exhibit patterns consistent with behavior; 2) when judging highly prosocial but unfair decisions, as the social distance between the decision-maker and the participant decreases, the participant's moral rating of the decision decreases, but their willingness to cooperate increases, demonstrating a dissociation between moral rating and willingness to cooperate. This study suggests that in judging complex moral decisions with multiple components, prosociality and fairness are not independent but interactively influence judgments together. The study reveals the flexibility of moral judgments and the interactions between various moral factors, providing new insights into the psychological mechanisms of complex moral judgments in different social contexts.

Human moral reactions to artificial intelligence (AI) agents' behavior constitute an important aspect of modern-day human-AI relationships. Although previous studies have mainly focused on autonomy ethics, this study investigates how individuals judge AI agents' violations of community ethics (including betrayals and subversions) compared with human violations. Participants' behavioral responses, event-related potentials (ERPs), and individual differences were assessed. Behavioral findings reveal that participants rated AI agents' community-violating actions less morally negative than human transgressions, possibly because AI agents are commonly perceived as having less agency than human adults. The ERP N1 component showed the same pattern with moral rating scores, indicating the modulation effect of human-AI differences on initial moral intuitions. Moreover, the level of social withdrawal correlated with a smaller N1 in the human condition but not in the AI condition. The N2 and P2 components were sensitive to the difference between the loyalty/betrayal and authority/subversion domains but not human/AI differences. Individual levels of moral sense and autistic traits also influenced behavioral data, especially on the loyalty/betrayal domain. In our opinion, these findings offer insights for predicting moral responses to AI agents and guiding ethical AI development aligned with human moral values.

Considering the crucial role of morality in shaping one’s reputation, exploring factors that modulate people’s decision to share morally salient news is important. Previous studies suggested that self-expression and socializing are 2 key factors for news-sharing behaviors, suggesting the key role of anonymity in such decisions. Using functional magnetic resonance imaging (fMRI) and transcranial direct current stimulation (tDCS), the present study focused on how anonymity modulates the sharing of morally salient information, as well as its neural mechanisms. Results showed that compared to moral news, people were more reluctant to share immoral news, especially when they share it with their real names shown. On the neural level, we found that this effect was associated with the activity of the left temporoparietal junction (TPJ), as well as its functional connection to its right counterpart. Dynamic causal modeling analysis revealed the moral valence of news and the anonymity of sharing modulated the effective connectivity between the left TPJ and the middle frontal gyrus as well as the medial frontal gyrus. There was no significant difference when sharing news anonymously. Further, a followed-up tDCS experiment supported the causal role of the left TPJ in this behavioral effect. Taken together, these results suggested that people concern more about social repercussion, when they share the news with their real-names shown, especially when sharing immoral news, and this effect is associated with stronger neural activation in the left TPJ, as well as changes in its functional connectivity with other brain regions.

In real life, it is not unusual that we face potential threats (i.e., physical stimuli and environments that may cause harm or danger) with other individuals together, yet it remains largely unknown how threat-induced anxious feelings influence prosocial behaviors such as resource sharing. In this study, we investigated this question by combining functional magnetic resonance imaging and a novel paradigm. Together with an anonymous partner, each participant faced the possibility of receiving a 10-s noise administration, which had a low or high probability to be a threat (i.e., the intensity of noise can induce a high level of unpleasantness). Each participant first reported her/his immediate feeling of anxiety about the current situation (being threatened by the unpleasant noise), then decided how to split a number of resources (which could relieve the noise) between her/him and the partner. Behavioral results revealed that the participants showed a selfish bias in the threat conditions than in the safe conditions, and that self-reported anxiety feeling significantly predicted this bias. Functional magnetic resonance imaging results revealed that: (1) the activation level of the anterior insula was correlated with self-reported anxiety and (2) the connectivity between the anterior insula and the temporoparietal junction was sensitive to the modulating effect of anxiety on the selfish bias. These findings indicate the neural correlates of the association between threat-induced anxiety and prosocial tendencies in social interactions.

Resource scarcity pervades our life. A scarcity mindset triggered by perceiving insufficient resources has been proven to influence our cognition and behaviors, yet it remains unknown whether this mindset specifically influences empathy. The present study induced feelings of scarcity or abundance in separate groups of participants through experimental manipulation and examined the effects of both mindsets on the behavioral and neural responses to others' pain. Behaviorally, pain intensity ratings of others' pain were lower in the scarcity group than in the abundance group. The analysis of event-related potentials revealed that N1 amplitudes for painful and nonpainful stimuli were comparable in the scarcity group but differed significantly in the abundance group. Additionally, while both groups showed larger late positive potential amplitudes for painful stimuli than for nonpainful stimuli, this amplitude differential was significantly smaller in the scarcity group than in the abundance group. Thus, behavioral and neural evidence suggests that inducing a scarcity mindset significantly dampens the ability to empathize with others' pain during both the early and late stages of empathic processing. These findings shed light on our understanding of how a scarcity mindset may influence social emotions and behaviors.

Classical cavernous sinus embolism is a rare clinical finding, presented most commonly by complaints of headache, diplopia, visual field defects, facial pain, and progressive neurological deficits. Many patients exhibit symptoms of III, IV, and VI nerve palsies. We hereby report a rare case of aseptic cavernous sinus embolism developed in a 75-year-old male with primary lung cancer who presented with binocular diplopia due to unilateral third and sixth cranial nerve palsies with pupil-sparing. The possibility of cavernous sinus cancer embolus should be considered if the routine examination excluded metastases, infiltration, carcinomatous meningitis, or the paraneoplastic process. 18F-FDG PET imaging may provide a promising diagnostic modality for the diagnosis of cancer embolus.

People as third-party observers, without direct self-interest, may punish norm violators to maintain social norms. However, third-party judgment and the follow-up punishment might be susceptible to the way we frame (i.e., verbally describe) a norm violation. We conducted a behavioral and a neuroimaging experiment to investigate the above phenomenon, which we call the "third-party framing effect". In these experiments, participants observed an anonymous perpetrator deciding whether to keep her/his economic benefit while exposing a victim to a risk of physical pain (described as "harming others" in one condition and "not helping others" in the other condition), then they had a chance to punish that perpetrator at their own cost. Our results showed that the participants were more willing to execute third-party punishment under the harm frame compared to the help frame, manifesting a framing effect. Self-reported anger toward perpetrators mediated the relationship between empathy toward victims and the framing effect. Meanwhile, activation of the insula mediated the relationship between mid-cingulate cortex activation and the framing effect; the functional connectivity between these regions significantly predicted the size of the framing effect. These findings shed light on the psychological and neural mechanisms of the third-party framing effect.

Background: Endoplasmic reticulum stress (ERS) occurred in S63del mutant CMT1B mice model, and few drugs has been studied. Mesencephalic astrocyte-derived neurotrophic factor (MANF) can inhibit ERS. This study aimed at investigating the effect of MANF on ERS of RT4-D6P2T schwannoma cells with S63del MPZ Mutation. Methods: Experimental grouping: blank control group, blank control + MANF group, lentivirus group, lentivirus + MANF group, S63del MPZ group, S63del MPZ + MANF group. CCK8 and Annexin-FITC/PI were used to detect cell proliferation and apoptosis. JC-1 was used to detect ΔΨm. MANF, GRP78 and CHOP mRNA and protein were detected by using RT-qPCR, western blotting and immunofluorescence. ER-Tracker and mito-tracker were used to observe the morphology of endoplasmic reticulum (ER) and mitochondria. Results: Cell proliferation decreased (p < 0.001) and apoptosis increased (p < 0.001) in S63del MPZ group; cell proliferation increased (p = 0.005) and apoptosis decreased (p < 0.001) in S63del MPZ + MANF group. ΔΨm decreased (p < 0.001), MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase3 increased (p < 0.001) and Bcl2 decreased (p < 0.001) in S63del MPZ group. MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase3 decreased (p < 0.001) and Bcl2 increased (p < 0.001) in S63del MPZ group. Conclusions: ERS occurred in RT4-D6P2T cells with S63del MPZ mutation, and MANF exerted protective effect in RT4-D6P2T cells with S63del MPZ mutation.

People as third-party observers, without direct self-interest, may punish norm violators to maintain social norms. However, third-party judgment and the follow-up punishment might be susceptible to the way we frame (i.e., verbally describe) a norm violation. We conducted a behavioral and a neuroimaging experiment to investigate the above phenomenon, which we call “third-party framing effect.” In these experiments, participants observed an anonymous player A decided whether to retain her/his economic benefit while exposing player B to a risk of physical pain (described as “harming others” in one condition and “not helping others” in the other condition), then they had a chance to punish player A at their own cost. Participants were more willing to execute third-party punishment under the harm frame compared to the help frame, manifesting as a framing effect. Self-reported moral outrage toward player A mediated the relationship between empathy toward player B and the framing effect size. Correspondingly, the insula (possibly related to empathy) and cerebellum (possibly related to anger) were activated more strongly under the harm frame than the help frame. Functional connectivity between these regions showed strongest weight when predicting the framing effect size. These findings shed light on the psychological and neural mechanisms of the third-party framing effect. Graphic abstract

OBJECTIVE:This retrospective study analyzed the clinical characteristics and prognosis of the elderly amyotrophic lateral sclerosis (ALS) population in a large sample.METHODS:The study included 1,005 patients with sporadic ALS admitted to Chinese PLA General Hospital between March 2011 and March 2021. We stratified the ALS patients into young and old groups using 2 cutoffs for the age at disease onset (≥65 or ≥70 years old) and compared their demographic, clinical, and survival data.RESULTS:The mean onset age of all patients was 52.79 ± 10.55 years, with 123 (12.24%) having a disease onset ≥65 years and 44 (4.38%) having an onset ≥70 years. There were 624 (62.1%) male patients. More bulbar-onset cases were in the late-onset group (p = 0.001). The sex distribution, time from onset to diagnosis, and the time of symptom spread from spinal or bulbar localization to a generalized localization did not differ between groups. Late-onset patients progressed more rapidly and had a significantly shorter survival.CONCLUSIONS:Chinese ALS patients have an earlier age at onset and a relatively smaller proportion of old onset than European and Japanese patients. Elderly patients are more likely to have bulbar onset, which is related to rapid progression and a shorter survival.

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease involving the upper and lower motor neurons of the spinal cord, brainstem, and cerebral cortex. At least 30 genes have been implicated in familial ALS (fALS) and sporadic ALS (sALS). Kaneb et al. (2015) first carried out a large-scale sequencing study in ALS patients and identified two loss-of-function (LOF) variants in the GLE1 gene. The LOF mutation-induced disruption of RNA metabolism through the haploinsufficiency mechanism is implicated in ALS pathogenesis. A total of 628 ALS patients and 522 individuals without neurodegenerative disorders were enrolled in this study to explore the GLE1 gene contribution to ALS in the Chinese population. All 16 exons and the flanking intron of GLE1 were screened by Sanger sequencing. In total, we identified seven rare GLE1 coding variants, including one novel nonsense mutation and six rare missense mutations in 628 ALS patients. The frequency of GLE1 LOF mutations was 0.16% (1/628) among Chinese sALS patients, implying that it is an uncommon genetic determinant of ALS in Chinese patients. Additionally, the rare missense variants in the hCG1-binding domain of GLE1 impairing the distribution of the hGle1B isoform at the nuclear pore complex (NPC) region may be involved in the pathogenesis of ALS.

Mutations in the SH3TC2 gene cause Charcot–Marie–Tooth disease type 4C (CMT4C), characterized by inherited demyelinating peripheral neuropathy. CMT4C is a common form of CMT4/autosomal recessive (AR) CMT1. This study examined the SH3TC2 variants, investigated genotype–phenotype correlations and explored the frequency of CMT4C in Chinese patients. A total of 206 unrelated patients of Chinese Han descent clinically diagnosed with CMT were recruited. All patients underwent detailed history-taking, neurological examination, laboratory workups, and electrophysiological studies. Genetic analysis was performed via high-throughput target sequencing (NGS). Three patients, one male and two females, were found to carry five SH3TC2 mutations: patient 1 (c.3154C > T, p.R1054X; c.929G > A, p.G310E); Patient 2 (c.2872_2872del, p.S958fs; c.3710C > T, p.A1237V) and Patient 3 (c.2782C > T, p.Q928X; c.929G > A, p.G310E). The c.2872_2872del, c.3710C > T and c.2782C > T variants were not reported before. CMT4C caused by SH3TC2 mutation is a very common type of CMT4/AR CMT1. Three novel mutations, c.2872_2872del, c.3710C > T and c.2782C > T, were found in this study. Combination of clinical phenotype, nerve conduction studies, genetic analysis and bioinformatics analysis are of vital importance in patients suspected as CMT.

Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) are mostly unilateral and rarely spread to the bilateral cortex and meninges. We describe a case of MOG-immunoglobulin G (IgG) associated disorder (MOGAD) in a 39-year-old male with bilateral meningo-cortical involvement. The patient was hospitalized for epilepsy, fever, and headache. The initial MRI revealed abnormalities in the sulci of the bilateral frontal, temporal, and parietal lobes. He was considered to have infectious encephalitis and given empiric antibiotic and antiviral therapy, which were ineffective. His condition rapidly improved after the patient was switched to high-dose immunoglobulin therapy. No tests supported the presence of central nervous system (CNS) infections or autoimmune encephalitis. The second and third MRI scans showed reduced but still clearly observable meningo-cortical lesions. The patient was discharged without a definite diagnosis, but reported severe left vision impairment 25 days later. A fourth MRI showed signs typical of demyelinating CNS disease in addition to the original meningo-cortical lesions. The patient's symptoms were initially relieved by low-dose corticosteroid therapy, but they eventually returned, and he was re-admitted. The original lesions were diminished on the fifth MRI scan, but new lesions had developed in the deep white matter. A positive cell-based assay for MOG-IgG in serum confirmed MOGAD. The patient received high-dose corticosteroid treatment followed by an oral methylprednisolone taper, and his visual acuity gradually improved. The sixth and final MRI showed substantial decreases in the original lesions without new lesion formation. This unique case presents the complete diagnosis and treatment process for MOGAD with bilateral meningo-cortical involvement and may provide a reference for prompt diagnosis.

The present study combined a novel hypothetical investment game with functional magnetic resonance imaging to examine how moral conflict biases our real decision preference when it is not obvious or explicitly presented. Investment projects were chosen based on their prior subjective morality ratings to fit into 2 categories: a high level of moral conflict (HMC) or a low level of moral conflict (LMC). Participants were instructed to invest high or low amounts of capital into different projects. Behavioral and neural responses during decision making were recorded and compared. Behaviorally, we observed a significant decision bias such that investments were lower for HMC projects than for LMC projects. At the neural level, we found that moral conflict-related activity in the anterior cingulate cortex (ACC) was higher in the HMC condition than in the LMC condition and that reward-related activity in bilateral striatum was lower. Dynamic causal modeling further suggested that the moral conflict detected in the ACC influenced final decisions by modulating the representation of subjective value through the ACC's connection to the reward system.

Objective: The aim of this study was to measure both plasma and cerebrospinal fluid (CSF) TAR DNA-binding protein 43 (TDP-43) and phosphorylated TDP-43 (pTDP-43) levels in sporadic amyotrophic lateral sclerosis (sALS) patients, and to compare them with that of healthy controls. The correlation between plasma or CSF TDP-43/pTDP-43 and clinical indicators of ALS patients was assessed. Methods: Paired plasma and CSF TDP-43/pTDP-43 levels in 69 ALS patients and 59 healthy controls were measured by sandwich ELISA. Time to generalization (TTG), an indicator suggested that the time of symptoms spreading from spinal or bulbar localization to both, was evaluated in all patients screened for mutations in genes associated with ALS. Results: Both of the plasma TDP-43 and pTDP-43 levels were significantly higher in ALS patients than HCs ( P < 0.001). The pTDP-43/TDP-43 ratios in plasma were significantly higher in HCs than ALS patients ( P < 0.001). The area under the curve (AUC) value was 0.924 for plasma TDP-43 level, with a 91.3% sensitivity and 91.5% specificity. Moreover, the correlation between plasma and CSF TDP-43 was observed in each ALS patient ( r = 0.195, P = 0.027). A correlation between CSF pTDP-43 levels and the ALSFRS-R ( r = −0.245; P = 0.042) was established. A correlation was observed between plasma TDP-43 levels and TTG in ALS patients, which indicated that high levels of plasma TDP-43 correlated with prolonged TTG ( r = 0.415; P = 0.004). Conclusion: The plasma TDP-43 and pTDP-43 levels might play an important role in diagnosis in the future study of ALS. The plasma TDP-43 might differentiate ALS and HC groups based on high sensitivity and specificity, and as an indicator of progression of disease.

Objectives: In the present study, inflammatory factors, including interleukin (IL) and tumor necrosis factor-α (TNF-α) in the peripheral blood of patients with sporadic amyotrophic lateral sclerosis (sALS), were evaluated, and the issue of whether these variables were associated with the progression and severity of the disease examined. Methods: Data on inflammatory factors, including IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α, were retrospectively collected from 248 sALS patients admitted to the Chinese PLA General Hospital between March 2018 and March 2021. The relationships between the variables and clinical features, including gender, age at onset, site of onset, time from onset to hospital admission, ALS functional rating scale score, and diagnostic category were analyzed. Results: IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α levels were elevated in 43.75%, 7.04%, 16.42%, 25.35%, 1.41%, and 50.72% of ALS patients, respectively, compared with the normal value range. IL-2 and IL-6 levels were inversely associated with the ALS functional rating scale score (r = −0.280, p = 0.004 and r = −0.198, p = 0.048). Conclusion: Elevated levels of inflammatory cytokines support the hypothesis of an inflammatory response in ALS, and IL-2 and IL-6 may be used as an inflammation-related biomarker for disease severity.

Hereditary spastic paraplegias are heterogeneous disorders with diversified clinical manifestations, and genetic testing is important for the diagnosis and typing of hereditary spastic paraplegias. Gene panel sequencing containing 55 hereditary spastic paraplegias-related genes was performed to screen the pathogenic genes for hereditary spastic paraplegias. Sanger sequencing was adopted to validate if the family member carried the same pathogenic gene as the proband. Fifteen out of 53 patients carried mutation(s) in the screened hereditary spastic paraplegias-related genes. Among the 23 identified mutations, only one mutation had been previously reported as a pathogenic mutation. In the pedigree of case 6, the proband, his mother and uncle all carried the same novel deletion mutation (c.1459delA) at SPAST gene. Based on the pedigree, the disease was inherited in an AD pattern. In the pedigree of case 53, the family disease may be in an X-linked recessive inheritance pattern. The proband (case 53) carried two novel mutations in ALT1 gene and L1CAM gene (c.2511C>A), respectively. The L1CAM gene is the causative gene for the SPG1 X-linked recessive-hereditary spastic paraplegias. Our data confirm the genetic heterogeneity of hereditary spastic paraplegias, and SPG4/SPAST were the most frequent forms. The pathogenicity of the novel mutations is worth to be further investigated.