Regulatory B (Breg) cells represent a population of suppressor B cells that participate in immunomodulatory processes and inhibition of excessive inflammation. The regulatory function of Breg cells ...have been demonstrated in mice and human with inflammatory diseases, cancer, after transplantation, and particularly in autoinflammatory disorders. In order to suppress inflammation, Breg cells produce anti-inflammatory mediators, induce death ligand-mediated apoptosis, and regulate many kinds of immune cells such as suppressing the proliferation and differentiation of effector T cell and increasing the number of regulatory T cells. Central nervous system Inflammatory demyelinating diseases (CNS IDDs) are a heterogeneous group of disorders, which occur against the background of an acute or chronic inflammatory process. With the advent of monoclonal antibodies directed against B cells, breakthroughs have been made in the treatment of CNS IDDs. Therefore, the number and function of B cells in IDDs have attracted attention. Meanwhile, increasing number of studies have confirmed that Breg cells play a role in alleviating autoimmune diseases, and treatment with Breg cells has also been proposed as a new therapeutic direction. In this review, we focus on the understanding of the development and function of Breg cells and on the diversification of Breg cells in CNS IDDs.
Multimodal functional neuroimaging by combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) or magnetoencephalography (MEG) is able to provide high spatiotemporal ...resolution mapping of brain activity. However, the accuracy of fMRI‐constrained EEG/MEG source imaging may be degraded by potential spatial mismatches between the locations of fMRI activation and electrical source activities. To address this problem, we propose a novel fMRI informed time‐variant constraint (FITC) method. The weights in FITC are determined by combining the fMRI activities and electrical source activities in a time‐variant manner to reduce the impact of the fMRI extra sources. The fMRI weights are modified using cross‐talk matrix and normalized partial area under the curve to reduce the impact of fMRI missing sources. Monte Carlo simulations were performed to compare the source estimates produced by L2‐minimum norm estimation (MNE), fMRI‐weighted minimum norm estimation (fMNE), FITC, and depth‐weighted FITC (wFITC) algorithms with various spatial mismatch conditions. Localization error and temporal correlation were calculated to compare the four algorithms under different conditions. The simulation results indicated that the FITC and wFITC methods were more robust than the MNE and fMNE algorithms. Moreover, FITC and wFITC were significantly better than fMNE under the fMRI missing sources condition. A human visual‐stimulus EEG, MEG, and fMRI test was performed, and the experimental data revealed that FITC and wFITC displayed more focal areas than fMNE and MNE. In conclusion, the proposed FITC method is able to better resolve the spatial mismatch problems encountered in fMRI‐constrained EEG/MEG source imaging.
Emotions involve subjective experiences, behavioral performances, and physiological responses. Research concerning autonomic states corresponding to different emotions has prevailed for several ...decades. The present study was designed to investigate how specific emotions influence cardiac activities that reflect autonomic responses. Affective videos selected from a standardized Chinese database were used to induce amused, fearful, angry, and neutral emotions, while electrocardiogram and self-rated emotional experiences were recorded. Heart rate was significantly lower in the amused condition than in the angry, fearful and neutral condition. There were no significant differences among the latter three conditions. The root mean square of successive differences, an index of heart rate variability (HRV), was significantly larger in the amused condition than in the fearful, neutral, and angry conditions. It was also significantly larger in the angry condition than in the fearful condition. There were no significant differences between the fearful and neutral, or angry and neutral conditions. These results revealed that: (1) amusement activates the parasympathetic nervous system, and (2) compared with fear, anger is more likely to be linked with parasympathetic activation. We suggest that HRV, rather than the valence dimension (i.e., positive or negative) be regarded as a potential index to discriminate emotions related to approach or avoidance motivation.
There is considerable evidence that people are especially sensitive to emotionally negative materials. However, the temporal course of the negativity bias is still unclear. To address this issue, we ...observed the changes of P2, late positive components (LPC) and lateralized readiness potential (LRP) under positive, negative and neutral conditions, with International Affective Picture System (IAPS) pictures as emotional stimuli. We found that the amplitude of P2 in the negative block was significantly larger than that in the positive block, indicating that the attentional negativity bias occured very early in emotion perception. The LPC amplitude evoked by negative pictures was larger than that by positive and neutral pictures, suggesting that the negativity bias also occurred in a later evaluation stage of emotion processing. The response-locked LRP interval was shortest in the block of negative pictures, indicating that the negative contents elicited a reaction priming effect. Above all, this research showed that emotional negativity bias could occur in several temporal stages distinguished by attention, evaluation and reaction readiness periods.
Autobiographical memory (AM) is an important psychological phenomenon that has significance for self-development and mental health. The psychological mechanisms of emotional AM retrieval and their ...association with individual emotional symptoms remain largely unclear in the literature. For this purpose, the current study provided cue words to elicit emotional AMs. Event-related potentials (ERPs) associated with the retrieval process of AMs were recorded and analyzed. We found that the ERP component N400 was sensitive to both emotional valence and retrieval state, such that its amplitude was larger for negative compared to positive AMs, and larger responses for unrecalled compared to recalled AMs. Further, the N400 amplitude in the positive recalled condition was correlated with individual difference in depression (measured by the Beck Depression Inventory). Another ERP component, the late positive potential (LPP), was also sensitive to emotional valence, such that its amplitude was larger (i.e., more positive-going) for positive compared to negative cues. No significant effect was observed on the early ERP components P1, N1, or P2. The current findings bring new understanding on the difference between positive and negative AMs retrieval in the time domain. Also, the importance of this difference to the individual level of depression is worth noting.
Abstract
Men and women process language differently, but how the brain functions to support this difference is poorly understood. A few studies reported sex influences on brain activation for ...language, whereas others failed to detect the difference at the functional level. Recent advances of brain network analysis have shown great promise in picking up brain connectivity differences between sexes, leading us to hypothesize that the functional connections among distinct brain regions for language may differ in males and females. To test this hypothesis, we scanned 58 participants’ brain activities (28 males and 30 females) in a semantic decision task using functional magnetic resonance imaging. We found marked sex differences in dynamic interactions among language regions, as well as in functional segregation and integration of brain networks during language processing. The brain network differences were further supported by a machine learning analysis that accurately discriminated males from females using the multivariate patterns of functional connectivity. The sex-specific functional brain connectivity may constitute an essential neural basis for the long-held notion that men and women process language in different ways. Our finding also provides important implications for sex differences in the prevalence of language disorders, such as dyslexia and stuttering.
Short-term memory deficits have been associated with prefrontal cortex (PFC) dysfunction in Alzheimer's disease (AD) and AD mouse models. Extratelencephalic projection (ET) neurons in the PFC play a ...key role in short-term working memory, but the mechanism between ET neuronal dysfunction in the PFC and short-term memory impairment in AD is not well understood. Here, using fiber photometry and optogenetics, we found reduced neural activity in the ET neurons in the medial prefrontal cortex (mPFC) of the 5×FAD mouse model led to object recognition memory (ORM) deficits. Activation of ET neurons in the mPFC of 5×FAD mice rescued ORM impairment, and inhibition of ET neurons in the mPFC of wild type mice impaired ORM expression. ET neurons in the mPFC that project to supramammillary nucleus were necessary for ORM expression. Viral tracing and in vivo recording revealed that mPFC ET neurons received fewer cholinergic inputs from the basal forebrain in 5×FAD mice. Furthermore, activation of cholinergic fibers in the mPFC rescued ORM deficits in 5×FAD mice, while acetylcholine deficiency reduced the response of ET neurons in the mPFC to familiar objects. Taken together, our results revealed a neural mechanism behind ORM impairment in 5×FAD mice.
Oral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ...ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy.
We retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded.
Both IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066-2.975; p = 0.028). All the adverse events were transient and tolerable.
Our findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.
Abstract
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.
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