This work proposes an intrinsically explainable, straightforward method to decode P300 waveforms from electroencephalography (EEG) signals, overcoming the black box nature of deep learning techniques. The proposed method allows convolutional neural networks to decode information from images, an area where they have achieved astonishing performance. By plotting the EEG signal as an image, it can be both visually interpreted by physicians and technicians and detected by the network, offering a straightforward way of explaining the decision. The identification of this pattern is used to implement a P300-based speller device, which can serve as an alternative communication channel for persons affected by amyotrophic lateral sclerosis (ALS). This method is validated by identifying this signal by performing a brain-computer interface simulation on a public dataset from ALS patients. Letter identification rates from the speller on the dataset show that this method can identify the P300 signature on the set of 8 patients. The proposed approach achieves similar performance to other state-of-the-art proposals while providing clinically relevant explainability (XAI).

Fatigue is an extremely common symptom in in people with multiple sclerosis (PwMS) and has a severe impact on quality of life. The purpose of the present study was to verify whether fatigue in PwMS is associated with a selective covert attention impairment, as measured by event-related potentials and to assess whether it is more associated with an impairment of top-down or bottom-up attentional control. Twenty-two PwMS and fatigue-MSF, 17 without fatigue-MSnF and 35 healthy volunteers underwent a three-stimulus P300 novelty task that elicits both the P3a and the P3b components. P3b latency was comparable between groups, but PwMS, independently from the presence of fatigue displayed significantly greater P3b amplitudes. P3a latency was significantly prolonged in MSF alone, while P3a amplitude in MSnF group was greater than controls. MSF were able to categorize the task-relevant target stimulus but the orienting response to a novel salient stimulus was delayed, indicating an impairment in bottom-up attentional control mechanism related to ventral attention network. Fatigue is selectively associated with a covert attentional deficit related to the ability to reallocate attentional resources to salient stimuli, a crucial function of adaptive decision-making behaviour.

This study examined the neural signatures associated with conflict-monitoring, recognition and feedback processing in a feedback Concealed Information Test (fCIT), and also examined whether all the ERPs can be used to detect concealed autobiographical information. Participants were randomly assigned to one of two groups (guilty or innocent) and then tested in the fCIT while undergoing electroencephalograms (EEGs). The results showed that the probe (participants\' name) elicited a more negative N200, and a more positive recognition P300 than irrelevants among guilty participants. Additionally, feedback following the probe elicited a larger feedback P300 than feedback following irrelevants. Further, we found that three indicators, including the conflict-monitoring N200, recognition P300, and feedback P300, could significantly discriminate between guilty and innocent participants, whereas the FRN could not. Combining them is highly effective in discriminating between guilty and innocent participants (AUC = 0.91). These findings not only shed light on the neural processing of the fCIT but also suggest the potential of using the fCIT to detect concealed autobiographical information.

Economic decision-making plays a paramount role in both individual and national interests. Individuals have fairness preferences in economic decision-making, but a proposer\'s moral-related information may affect fairness considerations. In prior ERP studies, researchers have suggested moral identity influences fairness preferences in the Ultimatum Game (UG), but there are discrepancies in the results. Furthermore, whether role models (individuals whom someone else looks to help decide suitable behaviors), who can modulate people\'s moral standards, can affect fairness concerns in UG is still understudied. To address the questions, we selected the moral-related statements by eliminating those with illegal information and employed the ERP technique to explore whether the interplay of the proposer\'s role model and moral-related behavior influenced fairness processing in the modified UG and the corresponding neural mechanisms. We mainly found that the aforementioned interaction effect on proposal considerations in UG could be mirrored in both rejection rates and P300 variations. The results demonstrate that the interaction between the proposer\'s role model and moral behavior can modulate fairness concerns in UG. Our current work provides new avenues for elucidating the time course of the influencing mechanism of fair distributions in complicated social environments.

Virtual reality (VR) allows to create controlled scenarios in which the quantity of stimuli can be modulated, as happen in real-life, where humans are subjected to various multisensory-often overlapping-stimuli. The present research aimed to study changes in attentional processes within an auditory oddball paradigm during a virtual exploration, while varying the amount of distractors. Twenty healthy volunteers underwent electroencephalography (EEG) during three different experimental conditions: an auditory oddball without VR (No-VR condition), an auditory oddball during VR exploration without distractors (VR-Empty condition), and an auditory oddball during VR exploration with a high level of distractors (VR-Full condition). Event-related potentials (ERPs) were computed averaging epochs of EEGs and analyzing peaks at 100 ms (N100) and 300 ms (P300) latencies. Results showed modulation of N100 amplitude in Fz and of P300 amplitude in Pz. Statistically significant differences in latency were observed only for P300 where the latency results delayed from the No-VR to VR-Full. The scalp topography revealed for P100 no significant differences between frequent and rare stimuli in either the No-VR and VR-Empty conditions. However, significant results were found in N100 in VR-Full condition. For P300, results showed differences between frequent and rare stimuli, in every condition. However, this difference is gradually less widespread from No-VR condition to the VR-Full. The emerging integration of VR with EEG may have important implications for studying brain attentional processing.

The role of peroxisome proliferator-activated receptor (PPAR)β/δ in hepatic fibrosis remains a subject of debate. Here, we examined the effects of a PPARβ/δ agonist on the pathogenesis of liver fibrosis and the activation of hepatic stellate cells (HSCs), the main effector cells in liver fibrosis, in response to the pro-fibrotic stimulus transforming growth factor-β (TGF-β). The PPARβ/δ agonist GW501516 completely prevented glucose intolerance and peripheral insulin resistance, blocked the accumulation of collagen in the liver, and attenuated the expression of inflammatory and fibrogenic genes in mice fed a choline-deficient high-fat diet (CD-HFD). The antifibrogenic effect of GW501516 observed in the livers CD-HFD-fed mice could occur through an action on HSCs since primary HSCs isolated from Ppard-/- mice showed increased mRNA levels of the profibrotic gene Col1a1. Moreover, PPARβ/δ activation abrogated TGF-β1-mediated cell migration (an indicator of cell activation) in LX-2 cells (immortalized activated human HSCs). Likewise, GW501516 attenuated the phosphorylation of the main downstream intracellular protein target of TGF-β1, suppressor of mothers against decapentaplegic (SMAD)3, as well as the levels of the SMAD3 co-activator p300 via the activation of AMP-activated protein kinase (AMPK) and the subsequent inhibition of extracellular signal-regulated kinase-1/2 (ERK1/2) in LX-2 cells. Overall, these findings uncover a new mechanism by which the activation of AMPK by a PPARβ/δ agonist reduces TGF-β1-mediated activation of HSCs and fibrosis via the reduction of both SMAD3 phosphorylation and p300 levels.

Although many studies document the role of propositional truth-value in human psychological reading behavior, there is a relative paucity of research examining the role of differential propositional truth-value in processing Chinese counterfactual conditionals. This study is to investigate the role of differential propositional value in processing Chinese counterfactual conditionals by means of ERPs (event-related potentials). The study is based on comprehending two types of Chinese counterfactual conditionals, which is propositional truth value introduced by two different markers of conditional conjunctions in the protasis and apodosis, such as true counterfactual conditional markers jiaru (if) & jiu (so) in the sentence wo xiang yu jiaru you tui jiu keyi zai shuixia zhixi (I think if fish had legs so they could stifle under water), and false counterfactual conditional markers ruguo (if) & namo (then) in the sentence wo xiang gou ruguo you lin namo keyi zai shuixia huxi (I think if dogs had scales, then they could breathe under water). Two counterfactual propositional values (i.e. true and false propositional values) are constructed through manipulating sentence counterfactuality between the true and false counterfactual conditional markers in the protasis and the apodosis. Twenty-four full-time Chinese college students participated in the ERP study. The results demonstrated that processing the true counterfactual propositional sentences with conditional markers jiaru (if) & jiu (so) elicited the N400 effect relative to false propositional sentences with conditional markers ruguo (if) & namo (then). Moreover, the counterfactual sentences with true propositional conditions varied from the elicitation of the N400 effect in the protasis and absence of the N400 effect in the apodosis, showing that semantic roles may gradually disappear under the impact of truth value of propositional counterfactual condition, and/or the roles of semantic anomaly was eliminated in the accumulated sentence processing. While for the false counterfactual conditional sentences, elicitations of P300 in the protasis and robust N400 effect in the apodosis were shown, indicating the increasing semantic role in the processing. Interestingly, there was the absence of the P600 effect for processing sentences with syntactic violation, suggesting little extra syntactic cost in processing sentences with false propositional condition.

UNASSIGNED: Selective attention to auditory input is reflected in the brain by an electric amplitude called the P3b amplitude, which is measured using electroencephalography. Previous research has shown that children and adolescents with autism have an attenuated P3b amplitude when they have to attend specific sounds while ignoring other sounds. However, it is unknown whether a reduced P3b amplitude in autistic children and adolescents is associated with their autism features, daily functioning and/or cognitive functions. This study aimed to examine these questions. Therefore, we assessed selective attention to auditory input in 57 children with autism aged 7-14 years and 57 neurotypically developing controls while measuring their brain activity with electroencephalography. Participants further underwent cognitive assessment, and parents reported on autistic traits and daily functioning. As expected, children with autism had lower P3b amplitude compared to their neurotypical peers. Importantly, an attenuated P3b amplitude was associated with more parent-reported social-communication problems and difficulties with daily functioning. Children with autism further had reduced processing speed of visual input, which also was coupled to a lower P3b amplitude. In conclusion, we found attenuated P3b amplitude in children with autism performing an auditory selective attention task, which was related to difficulties with processing visual input and allocating attentional resources critical for social and daily functioning. The results suggest that autistic children are more vulnerable to being disturbed when the environment is filled with conflicting sensory input.

OBJECTIVE: To date the vast majority of research in the visual neurosciences have been forced to adopt a highly constrained perspective of the vision system in which stimuli are processed in an open-loop reactive fashion (i.e., abrupt stimulus presentation followed by an evoked neural response). While such constraints enable high construct validity for neuroscientific investigation, the primary outcomes have been a reductionistic approach to isolate the component processes of visual perception. In electrophysiology, of the many neural processes studied under this rubric, the most well-known is, arguably, the P300 evoked response. There is, however, relatively little known about the real-world corollary of this component in free-viewing paradigms where visual stimuli are connected to neural function in a closed-loop. While growing evidence suggests that neural activity analogous to the P300 does occur in such paradigms, it is an open question when this response occurs and what behavioral or environmental factors could be used to isolate this component.
METHODS: The current work uses convolutional networks to decode neural signals during a free-viewing visual search task in a closed-loop paradigm within an open-world virtual environment. From the decoded activity we construct fixation-locked response profiles that enable estimations of the variable latency of any P300 analogue around the moment of fixation. We then use these estimates to investigate which factors best reduce variable latency and, thus, predict the onset time of the response. We consider measurable, search-related factors encompassing top-down (i.e., goal driven) and bottom-up (i.e., stimulus driven) processes, such as fixation duration and salience. We also consider saccade size as an intermediate factor reflecting the integration of these two systems.
RESULTS: The results show that of these factors only saccade size reliably determines the onset time of P300 analogous activity for this task. Specifically, we find that for large saccades the variability in response onset is small enough to enable analysis using traditional ensemble averaging methods.
CONCLUSIONS: The results show that P300 analogous activity does occur during closed-loop, free-viewing visual search while highlighting distinct differences between the open-loop version of this response and its real-world analogue. The results also further establish saccades, and saccade size, as a key factor in real-world visual processing.

Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, persistently infects over 90% of the human adult population and is associated with several human cancers. To establish life-long infection, EBV tampers with the induction of type I interferon (IFN I)-dependent antiviral immunity in the host. How various EBV genes help orchestrate this crucial strategy is incompletely defined. Here, we reveal a mechanism by which the EBV nuclear antigen 3A (EBNA3A) may inhibit IFNβ induction. Using proximity biotinylation we identify the histone acetyltransferase P300, a member of the IFNβ transcriptional complex, as a binding partner of EBNA3A. We further show that EBNA3A also interacts with the activated IFN-inducing transcription factor interferon regulatory factor 3 that collaborates with P300 in the nucleus. Both events are mediated by the N-terminal domain of EBNA3A. We propose that EBNA3A limits the binding of interferon regulatory factor 3 to the IFNβ promoter, thereby hampering downstream IFN I signaling. Collectively, our findings suggest a new mechanism of immune evasion by EBV, affected by its latency gene EBNA3A.