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 arousal in the estimation of time-to-collision of threatening stimuli.

The accurate estimation of time-to-collision (TTC) is essential for the survival of organisms. Previous studies have revealed that the emotional properties of approaching stimuli can influence the estimation of TTC, indicating that approaching threatening stimuli are perceived to collide with the observers earlier than they actually do, and earlier than non-threatening stimuli. However, not only are threatening stimuli more negative in valence, but they also have higher arousal compared to non-threatening stimuli. Up to now, the effect of arousal on TTC estimation remains unclear. In addition, inconsistent findings may result from the different experimental settings employed in previous studies. To investigate whether the underestimation of TTC is attributed to threat or high arousal, three experiments with the same settings were conducted. In Experiment 1, the underestimation of TTC estimation of threatening stimuli was replicated when arousal was not controlled, in comparison to non-threatening stimuli. In Experiments 2 and 3, the underestimation effect of threatening stimuli disappeared when compared to positive stimuli with similar arousal. These findings suggest that being threatening alone is not sufficient to explain the underestimation effect, and arousal also plays a significant role in the TTC estimation of approaching stimuli. Further studies are required to validate the effect of arousal on TTC estimation, as no difference was observed in Experiment 3 between the estimated TTC of high and low arousal stimuli.

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.

The temporal effect of uncertain context on the perceptual processing of painful and non-painful stimulation.

Uncertainty has been demonstrated to influence the perception of noxious stimuli, but little is known about the effects of prolonged uncertain contexts on the perception of painful and non-painful stimuli. To address this knowledge gap, the present study utilized a cue-based NPU-threat task, where uncertain and certain trials were separated into distinct blocks. The objective was to investigate the impact of uncertain contexts on the temporal dynamics of electroencephalogram (EEG) activity during the processing of painful and non-painful stimuli. The results revealed that the influence of uncertain contexts on neural responses extends beyond painful trials and is also evident in non-painful trials. In uncertain contexts, it has been observed that painful stimuli elicit larger P2 amplitudes and late beta band (13-30 Hz) event-related desynchronization (ERD) around 500-700 ms. However, in certain contexts, painful stimuli evoke stronger late gamma band (50-70 Hz) event-related synchronization (ERS) around 600-700 ms. For non-painful trials, in uncertain contexts, significantly higher amplitudes of the late positive potential (LPP) component and delta-theta band (2-7 Hz) ERS were observed compared to certain non-painful stimuli. These findings demonstrate that uncertain contexts exert a significant impact on the processing of both painful and non-painful stimuli, and this influence is mediated by distinct neural mechanisms.

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.

Insights into the Effects of Co-Regulated Factors on Li1.3Al0.3Ti1.7(PO4)3 Solid Electrolyte Preparation: Sources, Calcination Temperatures, and Sintering Temperatures.

The ionic conductivity, phase components, and microstructures of LATP depend on its synthesis process. However, their relative importance and their interactions with synthesis process parameters (such as source materials, calcination temperature, and sintering temperature) remain unclear. In this work, different source materials were used to prepare LATP via the solid-state reaction method under different calcination and sintering temperatures, and an analysis via orthogonal experiments and machine learning was used to systematically study the effects of the process parameters. Sintering temperatures had the greatest effect on the total ionic conductivity of LATP pellets, followed by the sources and calcination temperatures. Sources, as the foundational factors, directly determine the composition of a major secondary phase of LATP pellets, which influences the whole process. The calcination temperature had limited impact on the ion conductivity of LATP pellets if pellets were sintered under the optimal temperature. The sintering temperature is the most important factor that influences the ion conductivity by eliminating most secondary phases and altering the microstructure of LATP, including the intergranular contact, grain size, relative densities, etc. This work offers a novel perspective to comprehend the synthesis of solid-state electrolytes beyond LATP.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

CRISPR/Cas9­mediated EZH2 knockout suppresses the proliferation and migration of triple­negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive subtype of BC characterized by extensive intratumoral heterogeneity. Compared with other types of BC, TNBC is more prone to invasion and metastasis. The aim of the present study was to determine whether adenovirus-mediated clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 system is capable of effectively targeting enhancer of zeste homolog 2 (EZH2) in TNBC cells and lay an experimental basis for the investigation of the CRISPR/Cas9 system as a gene therapy for BC. In the present study, EZH2 was knocked out in MDA-MB-231 cells using the CRISPR/Cas9 gene editing tool to create EZH2-knockout (KO) group (EZH2-KO group). Moreover, the GFP knockout group (control group), and a blank group (Blank group), were employed. The success of vector construction and EZH2-KO were verified by T7 endonuclease I (T7EI) restriction enzyme digestion, mRNA detection and western blotting. Changes in proliferation and migration ability of MDA-MB-231 cells following gene editing were detected by MTT, wound healing, Transwell and in vivo tumor biology assays. As indicated by the results of mRNA and protein detection, the mRNA and protein expression of EZH2 were significantly downregulated in the EZH2-KO group. The difference in EZH2 mRNA and protein between the EZH2-KO and the two control groups was statistically significant. MTT, wound healing and transwell assay suggested that the proliferation and migration ability of MDA-MB-231 cells in the EZH2-KO group were significantly decreased after EZH2 knockout. In vivo, the tumor growth rate in the EZH2-KO group was significantly lower than that in the control groups. In brief, the present study revealed that the biological functions of tumor cells were inhibited after EZH2 knockout in MDA-MB-231 cells. The aforementioned findings suggested that EZH2 can have a key role in the development of TNBC.

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.

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.

The Functional Brain Network of Subcortical and Cortical Regions Underlying Time Estimation: An Functional MRI Study.

Time estimation is fundamental for human survival. There have been increasing studies suggesting that distributed brain regions, such as the basal ganglia, cerebellum and the parietal cortex, may contribute to a dedicated neural mechanism of time estimation. However, evidence on the specific function of the subcortical and cortical brain regions and the interplay of them is scare. In this work, we explored how the subcortical and cortical networks function in time estimation during a time reproduction task using functional MRI (fMRI). Thirty healthy participants performed the time reproduction task in both auditory and visual modalities. Results showed that time estimation in visual and auditory modality recruited a subcortical-cortical brain network including the left caudate, left cerebellum, and right precuneus. Besides, the superior temporal gyrus (STG) was found essential in the difference between time estimation in visual and auditory modality. Using psychophysiological interaction (PPI) analysis, we observed an increase in the connection between left caudate and left precuneus using the left caudate as the seed region in temporal reproduction task than control task. This suggested that the left caudate is the key region connecting and transmitting information to other brain regions in the dedicated brain network of time estimation.

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.

CAS(ME)3: A Third Generation Facial Spontaneous Micro-Expression Database With Depth Information and High Ecological Validity.

Micro-expression (ME) is a significant non-verbal communication clue that reveals one person's genuine emotional state. The development of micro-expression analysis (MEA) has just gained attention in the last decade. However, the small sample size problem constrains the use of deep learning on MEA. Besides, ME samples distribute in six different databases, leading to database bias. Moreover, the ME database development is complicated. In this article, we introduce a large-scale spontaneous ME database: CAS(ME) 3. The contribution of this article is summarized as follows: (1) CAS(ME) 3 offers around 80 hours of videos with over 8,000,000 frames, including manually labeled 1,109 MEs and 3,490 macro-expressions. Such a large sample size allows effective MEA method validation while avoiding database bias. (2) Inspired by psychological experiments, CAS(ME) 3 provides the depth information as an additional modality unprecedentedly, contributing to multi-modal MEA. (3) For the first time, CAS(ME) 3 elicits ME with high ecological validity using the mock crime paradigm, along with physiological and voice signals, contributing to practical MEA. (4) Besides, CAS(ME) 3 provides 1,508 unlabeled videos with more than 4,000,000 frames, i.e., a data platform for unsupervised MEA methods. (5) Finally, we demonstrate the effectiveness of depth information by the proposed depth flow algorithm and RGB-D information.

Effect of Concomitant Use of Analgesics on Prognosis in Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Background: Drug-drug interactions (DDIs) pose new challenges beyond traditional pharmacodynamics in the context of optimizing the treatment options with immune checkpoint inhibitors (ICIs). To alleviate cancer-related pain, analgesics are of absolute vital importance as chronic medications used by cancer patients. However, the possible outcome of ICI treatment concomitant with analgesics remains unclear. Methods: Original articles describing the possible influence of analgesics use on ICI treatment published before December 1, 2021 were retrieved from PubMed, Embase, and the Cochrane Library. Odds ratio (OR) with 95% confidence interval (CI) for objective response rate (ORR), hazard ratio (HR) with 95% CI for progression-free survival (PFS), and overall survival (OS) were calculated using the random-effects or fixed-effects model, and heterogeneity was assessed using the χ2-based Q-test. Publication bias was examined by funnel plot analysis. Results: A total of 11 studies involving 4,404 patients were included. The pooled OR showed that opioid use decreased the response of opioid users to ICIs compared to non-opioid users (OR = 0.49, 95% CI = 0.37-0.65, p < 0.001). Compared to patients who did not receive opioids, opioid users had an increased risk of progression and mortality (HR = 1.61, 95% CI = 1.37-1.89, p < 0.001; HR = 1.67, 95% CI =1.30-2.14, p < 0.001, respectively). Furthermore, the concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) was not significantly associated with differences in ORR, PFS, and OS in patients treated with ICIs (OR = 1.40, 95% CI = 0.84-2.32, p = 0.190; HR = 0.90, 95% CI = 0.77-1.06, p = 0.186; HR = 0.90, 95% CI = 0.71-1.14, p = 0.384, respectively). Conclusion: The concomitant use of opioids during ICI treatment has an adverse effect on patient prognosis, while the use of NSAIDs is not significantly associated with the prognosis in patients treated with ICIs.

Characteristics of the immunogenicity and tumor immune microenvironment in HER2-amplified lung adenocarcinoma.

Objective: Besides breast and gastric cancer, HER2 amplification/mutation are also found in lung adenocarcinoma (LUAD). However, the correlation between HER2 variations and the phenotype of immunogenicity and tumor immune microenvironment (TIME) in LUAD compared with breast and gastric cancer has yet to be fully elucidated. Methods: We integrated public databases (discovery set) and internal data (validated set) of 288 patients representing three distinct HER2-altered tumors. Genomic data were used to identify somatic mutations, copy number variations, and calculate tumor mutational burden (TMB) and microsatellite instability score. RNA sequencing was conducted to estimate immune gene signatures and contents of tumor-infiltrating immune cell populations. Finally, IHC was used to determine PD-L1 expression and the tumoral-infiltration of immune cells in 50 HER2-variant tumor specimens with no prior therapeutic regimens. Results: Compared with HER2-amplified breast and gastric cancers, patients with HER2-amplified LUAD showed higher immunogenicity, mainly manifested in immune checkpoints expression and tissue/blood TMB. Additionally, HER2-amplified LUAD exhibited an inflamed TIME with remarkably increased genes encoding HLAs, T-cell activity and immune cell-type, and accompanied with tumor-infiltrating lymphocytes. In LUAD, patients with HER2 amplification possessed higher tissue TMB than HER2 mutation, whereas no difference was observed in PD-L1 expression. HER2 amplification (primary) was associated with significantly higher PD-L1 expression and TMB than acquired HER2 amplification after resistance to EGFR-TKIs. Conclusion: Patients with HER2-amplified LUAD have better immunogenicity and/or an inflamed TIME among HER2-aberrant tumors. Our study may provide clues for establishing the benefits and uses of ICIs for patients with this disease.

Confusion Effects of Facial Expression Recognition in Patients With Major Depressive Disorder and Healthy Controls.

Facial expression recognition plays a crucial role in understanding the emotion of people, as well as in social interaction. Patients with major depressive disorder (MDD) have been repeatedly reported to be impaired in recognizing facial expressions. This study aimed to investigate the confusion effects between two facial expressions that presented different emotions and to compare the difference of confusion effect for each emotion pair between patients with MDD and healthy controls. Participants were asked to judge the emotion category of each facial expression in a two-alternative forced choice paradigm. Six basic emotions (i.e., happiness, fear, sadness, anger, surprise, and disgust) were examined in pairs, resulting in 15 emotion combinations. Results showed that patients with MDD were impaired in the recognition of all basic facial expressions except for the happy expression. Moreover, patients with MDD were more inclined to confuse a negative emotion (i.e., anger and disgust) with another emotion as compared to healthy controls. These findings highlight the importance that patients with MDD show a deficit of sensitivity in distinguishing specific two facial expressions.

Unpredictable fearful stimuli disrupt timing activities: Evidence from event-related potentials.

The present study investigated the effect of an imminent fearful stimulus on an ongoing temporal task. Participants judged the duration of a blank temporal interval followed by a fearful or a neutral image. Results showed an underestimation of the duration in the fearful condition relative to the neutral condition, but only when the occurrence of the fearful image was difficult to predict. ERPs results for the blank temporal interval found no effect of the fearful stimulus on the contingent negative variation (CNV) amplitude in the clock stage. However, after the image onset, there was a larger P1 for the fearful relative to the neutral condition. Although this effect was indistinguishable regardless of whether the fearful event could be easily predicted, a late positive potential (LPP) component displayed larger amplitude only for unpredictable fearful stimuli. The time-frequency results showed enhanced delta-theta power (0.5-7.5 Hz) for the unpredictable fearful stimuli in the late stage. Importantly, the enhanced delta-theta rhythm correlated negatively with the duration judgments. Together, these results suggest that an unpredictable fearful event might divert more attention away from the counting process in the working memory stage, resulting in missing ticks and temporal underestimation.