How mind wandering influences motor control: The modulating role of movement difficulty.

It has been found that mind wandering can impair motor control. However, it remains unclear whether the impact of mind wandering on motor control is modulated by movement difficulty and its associated neural mechanisms. To address this issue, we manipulated movement difficulty using handedness and finger dexterity separately in two signal-response tasks with identical experiment designs, in which right-handed participants performed key-pressing and key-releasing movements with the specified fingers, and they had to intermittently report whether their attention was "On task" or "Off task." Key-releasing with the right index finger (RI) had a faster reaction time and stronger contralateral delta-theta (1-7 Hz) functional connectivity than with the left index (LI) in Experiment 1, and mind wandering only reduced the contralateral delta-theta functional connectivity and midfrontal delta-theta activity for key-releasing with RI. Key-pressing with right index and middle fingers (RIR) had a faster reaction time and stronger midfrontal delta-theta activity than with right index and ring fingers (RIR) in Experiment 2, and mind wandering only reduced the midfrontal delta-theta activity for key-pressing with RIM. Theta oscillations are vital in motor control. These findings suggest that mind wandering only impairs the motor control of relatively simple movements without affecting the difficult ones. It supports the notion that mind wandering competes for executive resources with the primary task. Moreover, the quantity of executive resources recruited for a task and how these resources are allocated is contingent upon the task difficulty, which may determine whether mind wandering would interfere with motor control.

The role of self-related information in the sense of agency.

Sense of agency (SoA) refers to the subjective experience of controlling one's actions and their subsequent consequences. The present study endeavors to investigate the impact of how different degrees of self-related stimuli as action outcomes on the sense of agency by observing the temporal binding effect. Results showed that self-related sound significantly altered temporal binding, notably influencing outcome binding. A post-hoc explanation model effectively elucidated the role of self-related information in the formation of the sense of agency.

Common intentional binding effects across diverse sensory modalities in touch-free voluntary actions.

The intentional binding effect refers to the phenomenon where the perceived temporal interval between a voluntary action and its sensory consequence is subjectively compressed. Prior research revealed the importance of tactile feedback from the keyboard on this effect. Here we examined the necessity of such tactile feedback by utilizing a touch-free key-press device without haptic feedback, and explored how initial/outcome sensory modalities (visual/auditory/tactile) and their consistency influence the intentional binding effect. Participants estimated three delay lengths (250, 550, or 850 ms) between the initial and outcome stimuli. Results showed that regardless of the combinations of sensory modalities between the initial and the outcome stimuli (i.e., modal consistency), the intentional binding effect was only observed in the 250 ms delay condition. This findings indicate a stable intentional binding effect both within and across sensory modalities, supporting the existence of a shared mechanism underlying the binding effect in touch-free voluntary actions.

Word Familiarity Modulates the Interference Effects of Mind Wandering on Semantic and Reafferent Information Processing.

It has been found that mind wandering interferes with the sensory and cognitive processing of widespread stimuli. However, it remains unclear what factors can modulate the magnitude of the interference effects of mind wandering. Here, we investigate whether and how word familiarity modulates the interference effects of mind wandering on semantic and reafferent information processing. High- and low-frequency words were used as stimuli to induce high- and low-familiarity contexts in a sustained attention to response task, in which participants were required to respond to Chinese nonanimal words (nontarget) and withhold responses to Chinese animal words (target) as well as to intermittently report whether their state was "on task" or "off task." Behavioral results revealed lower reaction stability for both high- and low-frequency nontarget words preceding "off-task" reports than those preceding "on-task" reports. However, ERP results revealed that low-frequency rather than high-frequency words elicited more negative N400, attenuated late positive complex, and attenuated reafferent potential for "off-task" reports than for "on-task" reports. The results suggest that mind wandering makes semantic extraction and integration more difficult for unfamiliar but not familiar two-character Chinese words and attenuates the reafferent feedback of the motor response. These findings are consistent with the decoupling hypothesis of mind wandering and provide the first neural evidence for how familiarity with external stimuli modulates the interference effects of mind wandering.

Decoding the temporal representation of facial expression in face-selective regions.

The ability of humans to discern facial expressions in a timely manner typically relies on distributed face-selective regions for rapid neural computations. To study the time course in regions of interest for this process, we used magnetoencephalography (MEG) to measure neural responses participants viewed facial expressions depicting seven types of emotions (happiness, sadness, anger, disgust, fear, surprise, and neutral). Analysis of the time-resolved decoding of neural responses in face-selective sources within the inferior parietal cortex (IP-faces), lateral occipital cortex (LO-faces), fusiform gyrus (FG-faces), and posterior superior temporal sulcus (pSTS-faces) revealed that facial expressions were successfully classified starting from ∼100 to 150 ms after stimulus onset. Interestingly, the LO-faces and IP-faces showed greater accuracy than FG-faces and pSTS-faces. To examine the nature of the information processed in these face-selective regions, we entered with facial expression stimuli into a convolutional neural network (CNN) to perform similarity analyses against human neural responses. The results showed that neural responses in the LO-faces and IP-faces, starting ∼100 ms after the stimuli, were more strongly correlated with deep representations of emotional categories than with image level information from the input images. Additionally, we observed a relationship between the behavioral performance and the neural responses in the LO-faces and IP-faces, but not in the FG-faces and lpSTS-faces. Together, these results provided a comprehensive picture of the time course and nature of information involved in facial expression discrimination across multiple face-selective regions, which advances our understanding of how the human brain processes facial expressions.

Acute psychosocial stress weakens the sense of agency in healthy adults.

The sense of agency (SoA) refers to the feeling of being in control of one's actions and the subsequent consequence of these actions. Emotional context seems to alter the strength of sense of agency. The present study explored the influence of acute psychosocial stress on the SoA by means of the Trier Social Stress Test (TSST). Self-assessment manikin (SAM) and objective physiological indicators (e.g. heart rate, electrodermal activity, and salivary cortisol levels) were utilized to evaluate the effect of the TSST. We also employed the temporal binding effect as an implicit assessment of the participant's SoA. The results indicated that the stress level of the experimental group after TSST was significantly higher than the control group, whilst the temporal binding scores of the experimental group decreased after TSST manipulation. In short, acute psychosocial stress with intense emotional arousal weakened the sense of agency.

Multisensory transfer effects in implicit and explicit category learning.

In category learning, transfer emerges when individuals apply the knowledge or strategy learned with one set of stimuli to a novel set. Under multisensory circumstances, it remains unclear whether the transfer occurs differently in implicit and explicit category learning, as it remains controversial whether explicit knowledge is indispensable for transfer. To address this issue, we adopted multisensory stimuli in implicit (i.e., information integration, II) and explicit (i.e., conjunctive rule-based, RB) category learning tasks. Experiment 1 showed that when training and novel sets shared the same feature modalities, spontaneous transfer without feedback was perfect in the II condition but impaired in the RB condition. However, with feedback, the dependent transfer occurred equally between conditions. Experiment 2 revealed that when across different feature modalities, no spontaneous transfer was observed in any of the two conditions. A dependent transfer occurred in the RB but not in the II condition. Experiment 3 found that delayed feedback disrupted II task performance but not RB task performance, indicating that people did not learn the II task using an explicit rule. The current study demonstrated that transfer to novel stimuli could emerge in explicit and implicit category learning within feature modalities. However, the transfer across feature modalities could only arise with feedback in explicit learning. We further discuss these findings' meaning with the current category learning theory.

Disappearing and appearing: Temporal binding effects are consistent across situations.

Sense of agency refers to the feeling of control over actions and action outcomes. Previous studies were mostly confined to the situation of performing actions to make objects appear, while it remains unexplored whether we experience sense of agency when making objects disappear. Here, we examined the temporal binding effect, an implicit index of sense of agency, in performing actions to make objects disappear and compared the magnitude of this effect in the appearing and disappearing situations. Results showed that the temporal binding effect emerged when object's disappearances served as action outcomes. Moreover, the temporal binding effects in the appearing and disappearing situations did not differ significantly. Our findings extend the temporal binding effect to the situation of voluntarily making objects disappear, suggesting a comparable level of implicit sense of agency when voluntarily making objects disappear and appear.

Low serum Maresin-1 levels are associated with non-alcoholic fatty liver disease: a cross-sectional study.

BACKGROUND: Maresin-1 (MaR1) is an anti-inflammatory pro-resolving mediator and is considered a potential regulator of metabolic diseases. Non-alcoholic fatty liver disease (NAFLD) is a very common metabolic liver disease. However, little information is available on the relationship between MaR1 and NAFLD in humans. Therefore, the study explored the association between serum MaR1 levels and NAFLD. METHODS: A cross-sectional study was conducted in 240 Chinese people, including 116 non-NAFLD subjects and 124 NAFLD patients. Serum MaR1 levels were determined by enzyme-linked immunosorbent assay (ELISA). The association between MaR1 and NAFLD was assessed. RESULTS: Circulating MaR1 levels in NAFLD patients were markedly lower than those in non-NAFLD subjects (63.63 [59.87-73.93] vs 73.11 [65.12-84.50] pg/mL, P = 0.000). The percentages of patients with NAFLD gradually decreased with the increase of MaR1 quartiles (P < 0.001). Furthermore, serum MaR1 levels were positively associated with aspartate aminotransferase/alanine aminotransferase (AST/ALT), albumin, the albumin-globulin-ratio, and high-density lipoprotein cholesterol (HDL-C) (all P < 0.05) and negatively associated with body mass index (BMI), waist circumference, hip circumference, the waist-to-hip ratio, ALT, gamma-glutamyl transpeptidase (GGT), uric acid, triglyceride (TG), and fasting blood glucose (FBG) (all P < 0.05) after adjusting for sex and age. Binary logistic regression analysis revealed that serum MaR1 levels were significantly associated with NAFLD. CONCLUSIONS: Circulating MaR1 levels were decreased in patients with NAFLD, and a negative correlation was identified between NAFLD and serum MaR1 concentrations. Decreased MaR1 might be involved in the development of NAFLD.

TNF-α/IFN-γ profile of HBV-specific CD4 T cells is associated with liver damage and viral clearance in chronic HBV infection.

BACKGROUND & AIMS: The role of hepatitis B virus (HBV)-specific CD4 T cells in patients with chronic HBV infection is not clear. Thus, we aimed to elucidate this in patients with chronic infection, and those with hepatitis B flares. METHODS: Through intracellular IFN-γ and TNF-α staining, HBV-specific CD4 T cells were analyzed in 68 patients with chronic HBV infection and alanine aminotransferase (ALT) <2x the upper limit of normal (ULN), and 28 patients with a hepatitis B flare. HBV-specific HLA-DRB1*0803/HLA-DRB1*1202-restricted CD4 T cell epitopes were identified. RESULTS: TNF-α producing cells were the dominant population in patients' HBV-specific CD4 T cells. In patients with ALT <2xULN, both the frequency and the dominance of HBV-specific IFN-γ producing CD4 T cells increased sequentially in patients with elevated levels of viral clearance: HBV e antigen (HBeAg) positive, HBeAg negative, and HBV surface antigen (HBsAg) negative. In patients with a hepatitis B flare, the frequency of HBV core-specific TNF-α producing CD4 T cells was positively correlated with patients' ALT and total bilirubin levels, and the frequency of those cells changed in parallel with the severity of liver damage. Patients with HBeAg/HBsAg loss after flare showed higher frequency and dominance of HBV-specific IFN-γ producing CD4 T cells, compared to patients without HBeAg/HBsAg loss. Both the frequency and the dominance of HBV S-specific IFN-γ producing CD4 T cells were positively correlated with the decrease of HBsAg during flare. A differentiation process from TNF-α producing cells to IFN-γ producing cells in HBV-specific CD4 T cells was observed during flare. Eight and 9 HBV-derived peptides/pairs were identified as HLA-DRB1*0803 restricted epitopes and HLA-DRB1*1202 restricted epitopes, respectively. CONCLUSIONS: HBV-specific TNF-α producing CD4 T cells are associated with liver damage, while HBV-specific IFN-γ producing CD4 T cells are associated with viral clearance in patients with chronic HBV infection. LAY SUMMARY: TNF-α producing cells are the dominant population of hepatitis B virus (HBV)-specific CD4 T cells in patients with chronic HBV infection. This population of cells might contribute to the aggravation of liver damage in patients with a hepatitis B flare. HBV-specific IFN-γ producing CD4 T cells are associated with HBV viral clearance. Differentiation from HBV-specific TNF-α producing CD4 T cells into HBV-specific IFN-γ producing CD4 T cells might favor HBV viral clearance.

Icaritin promotes tumor T-cell infiltration and induces antitumor immunity in mice.

Icaritin, a hydrolytic product of icariin isolated from traditional Chinese herbal medicine genus Epimedium, has many pharmacological and biological activities. Here, we show that icaritin can effectively decrease tumor burden of murine B16F10 melanoma and MC38 colorectal tumors in a T-cell dependent manner. The treatment effects are associated with increased CD8 T-cell infiltration and increased effector memory T-cell frequency. In vivo depletion of CD8 T cell using an anti-CD8 monoclonal antibody abolished the antitumor effect, which supports the critical role of CD8 T cells during icaritin treatment. By analyzing immune cells in the tumor tissue, we found reduced frequency of CD11b+ Gr1+ myeloid-derived suppression cells (MDSCs) infiltration and downregulation of PD-L1 expression on MDSCs after icaritin treatment. This was not limited to MDSCs, as icaritin also decreased the expression of PD-L1 on neutrophils. Importantly, the combination of anti-PD-1/CTLA-4 and icaritin significantly enhances antitumor ability and increases the efficacy of either treatment alone. Our findings reveal that icaritin induces antitumor immunity in a CD8 T-cell-dependent way and justify further investigation of combining immune checkpoint therapy to icaritin-based antitumor therapy.

Implicit sequence learning of chunking and abstract structures.

The current study investigated whether people can simultaneously acquire knowledge about concrete chunks and abstract structures in implicit sequence learning; and whether the degree of abstraction determines the conscious status of the acquired knowledge. We adopted three types of stimuli in a serial reaction time task in three experiments. The RT results indicated that people could simultaneously acquire knowledge about concrete chunks and abstract structures of the temporal sequence. Generation performance revealed that ability to control was mainly based on abstract structures rather than concrete chunks. Moreover, ability to control was not generally accompanied with awareness of knowing or knowledge, as measured by confidence ratings and attribution tests, confirming that people could control the use of unconscious knowledge of abstract structures. The results present a challenge to computational models and theories of implicit learning.

Effects of task-irrelevant emotional information on deception.

Deception has been reported to be influenced by task-relevant emotional information from an external stimulus. However, it remains unclear how task-irrelevant emotional information would influence deception. In the present study, facial expressions of different valence and emotion intensity were presented to participants, where they were asked to make either truthful or deceptive gender judgments according to the preceding cues. We observed the influence of facial expression intensity upon individuals' cognitive cost of deceiving (mean difference of individuals' truthful and deceptive response times). Larger cost was observed for high intensity faces compared to low intensity faces. These results provided insights on how automatic attraction of attention evoked by task-irrelevant emotional information in facial expressions influenced individuals' cognitive cost of deceiving.

Voluntary action and tactile sensory feedback in the intentional binding effect.

The intentional binding effect refers to a subjective compression over a temporal interval between the start point initialized by a voluntary action and the endpoint signaled by an external sensory (visual or audio) feedback. The present study aimed to explore the influence of tactile sensory feedback on this binding effect by comparing voluntary key-press actions with voluntary key-release actions. In experiment 1, each participant was instructed to report the perceived interval (in ms) between an action and the subsequent visual sensory feedback. In this task, either the action (key-press or key-release) was voluntarily performed by the participant or a kinematically identical movement was passively applied to the left index finger of the participant. In experiment 2, we explored whether the difference in the perception of time was affected by the direction of action. In experiment 3, we developed an apparatus in which two parallel laser beams were generated by a laser emission unit and detected by a laser receiver unit; this allowed the movement of the left index finger to be detected without it touching a keyboard (i.e., without any tactile sensory feedback). Convergent results from all of the experiments showed that the temporal binding effect was only observed when the action was both voluntary and involved physical contact with the key, suggesting that the combination of intention and tactile sensory feedback, as a form of top-down processing, likely distracted attention from temporal events and caused the different binding effects.

Systemic C3 modulates CD8+ T cell contraction after Listeria monocytogenes infection.

Ag-specific CD8(+) T cell contraction (contraction), which occurs after the resolution of infection, is critical for homeostasis of the immune system. Although complement components regulate the primary CD8(+) T cell response, there is insufficient evidence supporting their role in regulating contraction and memory. In this study, we show that C3-deficient (C3(-/-)) mice exhibited significantly less CD8(+) T cell contraction than did wild-type mice postinfection with recombinant Listeria monocytogenes expressing OVA. Kinetic analyses also revealed decreased contraction in mice treated with cobra venom factor to deplete C3, which was consistent with the results in C3(-/-) recipient mice transplanted with bone marrow cells from the same donors as wild-type recipient mice. The phenotypes of memory cells generated by C3(-/-) mice were not altered compared with those of wild-type mice. Further, C5aR signaling downstream of C3 was not involved in the regulation of contraction. Moreover, the regulation of contraction by C3 may be independent of the duration of antigenic stimulation or the functional avidity of effector CD8(+) T cells. However, reduced contraction in C3(-/-) mice was accompanied by a decrease in the proportion of KLRG-1(hi) (killer-cell lectin-like receptor G1) CD127(lo) short-lived effector cells at the peak of the response and correlated with a reduction in the levels of inflammatory cytokines, such as IL-12 and IFN-γ, produced early postinfection. These results provide new insights into the role of systemic C3 in regulating contraction following intracellular bacterial infection and may help to develop vaccines that are more effective.

The role of edge-based and surface-based information in natural scene categorization: Evidence from behavior and event-related potentials.

A fundamental question in vision research is whether visual recognition is determined by edge-based information (e.g., edge, line, and conjunction) or surface-based information (e.g., color, brightness, and texture). To investigate this question, we manipulated the stimulus onset asynchrony (SOA) between the scene and the mask in a backward masking task of natural scene categorization. The behavioral results showed that correct classification was higher for line-drawings than for color photographs when the SOA was 13ms, but lower when the SOA was longer. The ERP results revealed that most latencies of early components were shorter for the line-drawings than for the color photographs, and the latencies gradually increased with the SOA for the color photographs but not for the line-drawings. The results provide new evidence that edge-based information is the primary determinant of natural scene categorization, receiving priority processing; by contrast, surface information takes longer to facilitate natural scene categorization.

Synchronous gastrointestinal cancer and gastrointestinal stromal tumors: a single-institution experience.

BACKGROUND: A study was conducted to investigate the clinicopathological features and survival outcomes of gastrointestinal stromal tumors (GISTs) that are synchronous with other gastrointestinal cancers. METHODS: Clinical and pathological data of 286 patients with primary GIST from a single institution from January 2009 to December 2014 were reviewed. RESULTS: The entire study population comprised 286 patients with GISTs. Of these patients, 167 (58.4%) were males and 119 (41.6%) were females. The median age was 58 years old (in the range 29-86 years). A total of 47 patients were diagnosed with GISTs synchronous with other digestive tract malignancies (synchronous group), whereas 239 patients were diagnosed with non-synchronous disease (non-synchronous group). The concomitant digestive tumors in 27, 12, 7, and 1 patients were diagnosed as gastric carcinoma, esophageal carcinoma, colorectal carcinoma, and pancreatic adenocarcinoma, respectively. Compared with the synchronous group, the non-synchronous group exhibited a higher percentage of increased mitotic count (P = 0.011). The difference in tumor diameter between the two groups was statistically significant (P < 0.001). Patients in the non-synchronous group exhibited larger tumor size than the patients in the synchronous group (5.9 ± 3.5 cm vs. 1.6 ± 0.4 cm, P < 0.001). The majority of GIST lesions in the synchronous group were located in the stomach (P = 0.020). Lower risk stratifications and worse ECOG performance statuses were observed in the synchronous group (P < 0.001) than in the non-synchronous group. The 5-year overall survival rate was significantly higher in patients with no synchronous digestive tract malignancies than in patients with synchronous disease (70.8 vs. 34.1%, P < 0.001). CONCLUSIONS: Patients with GIST synchronous with other gastrointestinal cancers show worse prognosis than those with non-synchronous tumors. Clinicians should pay more attention to this subgroup.

Exploring the Cognitive Processes Causing the Age-Related Categorization Deficit in the Recognition of Facial Expressions.

BACKGROUND/STUDY CONTEXT: Elderly people do not categorize emotional facial expressions as accurately as younger people, particularly negative emotions. Although age-related impairments in decoding emotions in facial expressions are well documented, the causes of this deficit are poorly understood. This study examined the potential mechanisms that account for this age-related categorization deficit by assessing its dependence on presentation time. METHODS: Thirty young (19-27 years old) and 31 older (68-78 years old) Chinese adults were asked to categorize the six basic emotions in facial expressions, each presented for 120, 200, 600, or 1000 ms, before and after exposure to a neutral facial expression. RESULTS: Shortened presentation times caused an age-related deficit in the recognition of happy faces, whereas no deficit was observed at longer exposure times. An age-related deficit was observed for all negative emotions but was not exacerbated by shorter presentation times. CONCLUSION: Age-related deficits in categorization of positive and negative emotions are caused by different mechanisms. Because negative emotions are perceptually similar, they cause high categorization demands. Elderly people may need more evidence in favor of the target emotion than younger people, and they make mistakes if this surplus of evidence is missing. In contrast, perceptually distinct happy faces were easily identified, and elderly people only failed when the presentation time was too short for their slower perceptual processing.

PD-1 deficiency enhances humoral immunity of malaria infection treatment vaccine.

Malaria infection treatment vaccine (ITV) is a promising strategy to induce homologous and heterologous protective immunity against the blood stage of the parasite. However, the underlying mechanism of protection remains largely unknown. Here, we found that a malaria-specific antibody (Ab) could mediate the protective immunity of ITV-immunized mice. Interestingly, PD-1 deficiency greatly elevated the levels of both malaria-specific total IgG and subclass IgG2a and enhanced the protective efficacy of ITV-immunized mice against the blood-stage challenge. A serum adoptive-transfer assay demonstrated that the increased Ab level contributed to the enhanced protective efficacy of the immunized PD-1-deficient mice. Further study showed that PD-1 deficiency could also promote the expansion of germinal center (GC) B cells and malaria parasite-specific TFH cells in the spleens of ITV-immunized mice. These results suggest that PD-1 deficiency improves the protective efficacy of ITV-immunized mice by promoting the generation of malaria parasite-specific Ab and the expansion of GC B cells. The results of this study provide new evidence to support the negative function of PD-1 on humoral immunity and will guide the design of a more effective malaria vaccine.

Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells.

By inhibiting target gene expression, microRNAs (miRNAs) play major roles in various physiological and pathological processes. miR-146a, a miRNA induced upon lipopolysaccharide (LPS) stimulation and virus infection, is also highly expressed in patients with immune disorders such as rheumatoid arthritis, Sjögren's syndrome, and psoriasis. Whether the high level of miR-146a contributes to any of these pathogenesis-related processes remains unknown. To elucidate the function of miR-146a in vivo, we generated a transgenic (TG) mouse line overexpressing miR-146a. Starting at an early age, these TG mice developed spontaneous immune disorders that mimicked human autoimmune lymphoproliferative syndrome (ALPS) with distinct manifestations, including enlarged spleens and lymph nodes, inflammatory infiltration in the livers and lungs, increased levels of double-negative T cells in peripheral blood, and increased serum immunoglobulin G levels. Moreover, with the adoptive transfer approach, we found that the B-cell population was the major etiological factor and that the expression of Fas, a direct target of miR-146a, was significantly dampened in TG germinal center B cells. These results indicate that miR-146a may be involved in the pathogenesis of ALPS by targeting Fas and may therefore serve as a novel therapeutic target.