Differentiating the DF effect in episodic memory: evaluating the contribution of the procedures of collaborative memory.

Existing research has demonstrated a significant directed forgetting (DF) effect in memory. However, it remains unclear whether this phenomenon would occur in the context of interpersonal collaboration. Additionally, the contribution of emotional valence to the DF effect in item memory and source memory (which are subtypes of episodic memory) also needs to be explored. To address these issues, we conducted two experiments that combined the collaborative memory paradigm with the item-method procedure of DF. In both experiments, positive, neutral, or negative words were presented as stimuli, each followed by an R/F cue during encoding. We conducted two recalls, labeled Recall 1 and Recall 2, which consisted of both memory tasks. Recall 1 was performed either individually or collaboratively, whereas Recall 2 was done individually. Experiment 1 and Experiment 2 adopted the free-flowing procedure and the turn-taking procedure of collaborative memory, respectively. We obtained three implications from our current findings. (a) The occurrence of the DF effect in item memory was found regardless of the procedure of collaborative memory, and it was insensitive to the emotional valence of words or to whether participants had collaborated or not. These patterns demonstrate that both the mechanisms of elaborative rehearsal and active suppression/encoding blocking were engaged across words of different emotional valences and in nominal and collaborative circumstances. (b) In source memory, the DF effect showed different patterns in ongoing and post-collaborative memory, which underpins the dual-process models. (c) The amplitude of the DF effect was sensitive to the interaction of emotional valence by the status of collaboration, and the impact of collaboration differed between the two experiments, offering telling evidence of different aspects of the retrieval strategy disruption hypothesis (RSDH). Directions for identifying more influential factors are put forward.

Does Expecting Matter? The Impact of Experimentally Established Expectations on Subsequent Memory Retrieval of Emotional Words.

Previous studies have confirmed that different degrees of expectation, including the bipolarity of the expected and unexpected, as well as an intermediate level (no expectation), can affect memory. However, only a few investigations have manipulated expectation through experimentally established schema, with no consideration of how expectation impacts both item and source memory. Furthermore, stimulus emotionality may also impact memory. Therefore, we conducted a study to investigate the effects of three levels of expectation on item and source memory while considering the impact of stimulus emotionality. The experiment began with a phase dedicated to learning the rules. In the subsequent study phase, negative and neutral words were manipulated as expected, no expectation, and unexpected, based on these rules. This was followed by tasks focused on item and source memory. The study found that there was a "U-shape" relationship between expectation and item memory. Additionally, the study revealed the distinct impacts of expectation on item and source memory. When it came to item memory, both expected and unexpected words were better remembered than those with no expectations. In source memory, expected words showed memory inferiority for expectation-irrelevant source information, but an advantage for expectation-relevant source information. Stimulus emotionality modulated the effect of expectation on both item and source memory. Our findings provide behavioral evidence for the schema-linked interactions between medial prefrontal and medial temporal regions (SLIMM) theory, which proposes that congruent and incongruent events enhance memory through different brain regions. The different patterns between item and source memory also support dual-process models. Moreover, we speculate that processing events with varying levels of emotionality may undermine the impact of expectation, as implied by other neural investigations.

Sensitivity of late ERP old/new effects in source memory to self-referential encoding focus and stimulus emotionality.

In episodic memory, the old/new effect, the contrast of the waveforms elicited by the correctly recognized studied items and the correctly rejected novel items, has been broadly concerned. However, the contribution of self-referential encoding to the old/new effect in source memory (i.e., source-SRE), is far from clarification; further, it remains unclear whether the contribution is susceptible to the factor of stimulus emotionality. To address these issues, adopting the event-related potential (ERP) technique, this study applied words of three types of emotional valences (positive, neutral, vs. negative) in the self-focus vs. external-focus encoding tasks. In the course of the test, four ERP old/new effects were identified: (a) the familiarity- and recollection-reflected mid-frontal effect (FN400) and late positive component (LPC) were both independent of source-SRE and stimulus emotionality; (b) the reconstruction-driven late posterior negativity (LPN) exhibited an adverse pattern of source-SRE and was susceptible to the emotional valence by encoding focus; and (c) the right frontal old/new effect (RFE), reflecting post-retrieval process, exhibited a source-SRE in emotional words. These effects provide compelling evidence for the influences of both stimulus valence and encoding focus on SRE in source memory, especially during the late processes. Further directions considering more perspectives are put forward.

Differentiation of the Contribution of Familiarity and Recollection to the Old/New Effects in Associative Recognition: Insight from Semantic Relation.

Previous research has revealed two different old/new effects, the early mid-frontal old/new effect (a.k.a., FN400) and the late parietal old/new effect (a.k.a., LPC), which relate to familiarity and recollection processes, respectively. Although associative recognition is thought to be more based on recollection, recent studies have confirmed that familiarity can make a great contribution when the items of a pair are unitized. However, it remains unclear whether the old/new effects are sensitive to the nature of different semantic relations. The current ERP (event-related potentials) study aimed to address this, where picture pairs of thematic, taxonomic, and unrelated relations served as stimuli and participants were required to discriminate the pair type: intact, rearranged, "old + new", or new. We confirmed both FN400 and LPC. Our findings, by comparing the occurrence and the amplitudes of these two components, implicate that the neural activity of associative recognition is sensitive to the semantic relation of stimuli and depends more on stimulus properties, that the familiarity of a single item can impact the neural activities in discriminating associative pairs, and that the interval length between encoding and test modulates the familiarity of unrelated pairs. In addition, the dissociation between FN400 and LPC reinforces the dual-process models.

Benefits and Detriments of Social Collaborative Memory in Turn-Taking and Directed Forgetting.

Collaborative recall by groups of people can evoke both memory detriments (e.g., collaborative inhibition) and benefits (e.g., error pruning and post-collaborative memory benefit). Yet, it remains indeterminate whether these effects are due to the emotional valence of stimuli and/or the specific subtypes of episodic memory tested (i.e., item memory and source memory), and whether they are related to the research procedure of directed forgetting (DF). We introduced item-method DF into collaborative memory research using a turn-taking procedure. The to-be-recalled words were studied in different emotional valences and were followed by either an R or F cue, which, respectively, instructed participants to remember or forget the words presented. We conducted two recall sessions (Recall 1 and Recall 2) that included the two subtypes of episodic memory. Recall 1 was performed either individually or collaboratively, while Recall 2 was always performed individually. We observed three major findings: (a) a collaborative memory decrement - collaborative inhibition - was minimally affected in both item memory and source memory tasks by either the emotional valence of the stimuli or the DF cue; (b) a collaborative memory benefit - error pruning of item memory - persisted within both ongoing and post-collaboration, while error pruning of source memory only presented in ongoing collaboration, thus demonstrating the relevance of dual-process models that differentiate automatic familiarity and effortful recollection processes; and (c) there was no post-collaborative memory benefit, indicating the importance of the type of collaborative procedure. We discuss these results in terms of various theories, including the retrieval strategy disruption hypothesis (RSDH) which asserts that memory strategies tend to be disrupted in collaboration but are facilitated within post-collaboration. Also, we describe the implications of these results and directions for exploring other influential factors in future research.

LPS-Induced Inflammation Affects Midazolam Clearance in Juvenile Mice in an Age-Dependent Manner.

PURPOSE: Inflammation has a significant impact on CYP3A activity. We hypothesized that this effect might be age dependent. Our objective was to conduct a population pharmacokinetic study of midazolam in mice at different developmental stages with varying degrees of inflammation to verify our hypothesis. METHODS: Different doses (2 and 5 mg/kg) of lipopolysaccharide (LPS) were used to induce different degrees of systemic inflammation in Swiss mice (postnatal age 9-42 days, n = 220). The CYP3A substrate midazolam was selected as the pharmacological probe to study CYP3A activity. Postnatal age, current body weight, serum amyloid A protein 1 (SAA1) levels and LPS doses were collected as covariates to perform a population pharmacokinetic analysis using NONMEM 7.2. RESULTS: A population pharmacokinetic model of midazolam in juvenile and adult mice was established. Postnatal age and current body weight were the most significant and positive covariates for clearance and volume of distribution. LPS dosage was the most significant and negative covariate for clearance. LPS dosage can significantly reduce the clearance of midazolam by 21.8% and 38.7% with 2 mg/kg and 5 mg/kg, respectively. Moreover, the magnitude of the reduction was higher in mice with advancing postnatal age. CONCLUSION: Both inflammation and ontogeny have an essential role in CYP3A activity in mice. The effect of LPS-induced systemic inflammation on midazolam clearance in mice is dependent on postnatal age.

Erratum: Sensitivity of Reality Monitoring to Fluency: Evidence from Behavioral Performance and Event-Related Potential (ERP) Old/New Effects.

Figure 1 is updated due to the mistake that occurred during the layout process. Reference: Aiqing Nie, Yueyue Xiao, Si Liu, Xiaolei Zhu, Delin Zhang. Sensitivity of Reality Monitoring to Fluency: Evidence from Behavioral Performance and Event-Related Potential (ERP) Old/New Effects. Med Sci Monit. 2019; 25: 9490-9498. 10.12659/MSM.917401.

Is there a self-positivity bias for destination memory? Behavioral and ERP evidence.

Despite extensive existing research concerning source memory (i.e., memory for what has been said, given, or done to us by whom) during social interaction, destination memory (i.e., memory for what we have said, given, or done to whom) remains to be explored. Furthermore, although destination memory is believed to involve a self-reference process, it remains unclear whether such a process is sufficient to trigger a self-positivity bias. To address these issues, we combined the destination memory paradigm with the social dilemma game to compare destination memory for cooperation and cheating. Both behavioral performance and the neural index of successful encoding, the Dm (difference due to memory) effect, were concerned. Behaviorally, destination memory for cooperative, cheating, and neutral behaviors decreased successively. For neural activities, the pre-400 ms Dm effects during 200-400 ms were non-significant under any condition. In the latency windows of 400-800 ms and 800-1000 ms, the post-400 ms Dm effects were reliably observed for both cooperative and cheating behaviors and were statistically comparable between the two behavior types, but the effect was not obtained for neutral behaviors. These data suggest a self-positivity bias in the behavioral performance but not in the encoding-related Dm effects of destination memory.

ERP Characteristics of Inducing Rule Validity in Number Series Under Time Pressure.

A great deal of research has been devoted to examining the neural mechanisms of inductive reasoning. However, the influences of rule validity and time pressure on numerical inductive reasoning remain unclear. In the current study, we aimed to examine the effects of these variables on the time course of rule identification in numerical inductive reasoning. We designed a 3 (task type: valid, invalid, and anomalous) × 2 (time pressure: with time pressure and without time pressure) within-subject experiment based on electroencephalographic event-related potentials (ERP). Behaviorally, we found significant effects of rule validity and time pressure on rule identification. Neurologically, we considered the elicited N200 ERP to reflect conflict detection and found it to be modulated by rule validity but not time pressure. We considered the induced P300 ERP to be primarily related to updating working memory, affected by both rule validity and time pressure. These findings have new implications for better understanding dynamic information processing within numerical inductive reasoning.

Professional discrepancies of doctors and lawyers in episodic memory: Modulations of professional morality and warning.

Past investigations have consistently demonstrated the robust stereotype-consistent effect in the circumstance of source memory but not always in item memory, including the case of professional stereotype. However, it remains unclear whether the effect still occurs in professional stereotype when considering the attributes of negative (or bad) or positive (or good); besides, it has not been concerned about how does warning work in remembering the professional stereotypical stimuli. The current experiments aimed to address these issues by adopting descriptive sentences as stimuli, which were related or unrelated to doctors and lawyers, and with different professional moral valences (negative, neutral, or positive). Item memory and source memory were tested successively. Experiment 1 without the explicit warning confirmed the reliable stereotype-consistent effect solely in source memory; the modulation of professional morality on memory behaved differently between doctor and lawyer, that is, negativity bias versus positivity bias. When giving an explicit warning (Experiment 2), the stereotype-consistent effect attenuated in the lawyer case, and the occurrence of negativity bias was sensitive to the memory task. Thus, our findings further reinforce the dual-process model; both professional morality and warning work in memory of professional stereotype, depending upon the nature of the profession, the concerned memory task, and also the presence of warning. Implications are made for future research to consider more perspectives.

Downregulation of Renal MRPs Transporters in Acute Lymphoblastic Leukemia Mediated by the IL-6/STAT3/PXR Signaling Pathway.

PURPOSE: Considering prior investigations on reductions of renal multidrug resistance-associated protein (MRP) 2 and 4 transporters in mice with acute lymphoblastic leukemia (ALL), we sought to characterize the underlying mechanisms responsible for IL-6/STAT3/PXR-mediated changes in the expression of MRP2 and MRP4 in ALL. SUBJECTS AND METHODS: ALL xenograft models were established and intravenously injected with methotrexate (MTX) of MRPs substrate in NOD/SCID mice. Protein expression of MRPs and associated mechanisms were detected by Western blotting and immunocytochemistry. Plasma concentrations of MTX were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: Plasma IL-6 levels in patients with newly diagnosed ALL were increased compared to children with pneumonia. Similarly, plasma IL-6 levels in ALL, ALL-tocilizumab (TCZ, an IL-6 receptor inhibitor) and ALL-S3I-201 (a selective inhibitor of STAT3) mice were increased compared to the control group. The MRP2, MRP4, and PXR expression in HK-2 cells treated with IL-6 were decreased, whereas the p-STAT3 expression was significantly increased compared to the control group results. These results are consistent with clearance of MRPs-mediated MTX in the ALL group. These effects were attenuated by blocking IL-6/STAT3/PXR signaling pathway. CONCLUSION: Inflammation-mediated changes in pharmacokinetics are thought to be executed through pathways IL-6-activated pathways, which can facilitate a better understanding of the potential for the use of IL-6 to predict the severity of adverse outcomes and the major implications on potential ALL treatments.

External (Versus Internal) Facial Features Contribute Most to Repetition Priming in Facial Recognition: ERP Evidence.

Previous event-related potential (ERP) research demonstrated four successive ERP components in the repetition priming of human face recognition: P100, N170, N250r, and N400. While these components correspond, respectively, to the four stages proposed by the interactive activation and competition (IAC) model, there has been no emphasis in past research on how internal and external facial features affect repetition priming and the sensitivity of these ERP components to item interval. This study was designed to address these issues. We used faces of celebrities as targets, including completely familiar faces, familiar internal feature faces, and familiar external feature faces. We displayed a target face either immediately following its prime (immediate repetition) or after a delay with interference from a presentation of two other faces (delayed repetition). ERP differences at P100 and N170 were nearly statistically non-significant; familiar faces and familiar external feature faces were associated with reliable ERP signals of N250r and N400 in the immediate repetition condition. For delayed repetition, however, N250r and N400 signals were only preserved for the familiar external feature faces. The differences of these ERP components suggest that, compared with internal facial features, external features of a previously presented face contribute more to brain-based facial repetition priming, particularly during the last two stages of the IAC model.

Extremely low dose of 6-mercaptopurine in a Chinese child with acute lymphoblastic leukaemia and multiple pharmacogenetic mutations.

WHAT IS KNOWN AND OBJECTIVES: Thiopurines are cornerstone drugs in the treatment of acute lymphoblastic leukaemia (ALL), but their use can be complicated by the incidence of life-threatening leucopenia. CASE DESCRIPTION: We describe a case of a 6-year-old Chinese boy with B-ALL receiving extremely low dose of 6-mercaptopurine (only 4% of recommended dose) during the ALL maintenance therapy phase. WHAT IS NEW AND CONCLUSION: Complex pharmacogenetic tests and TDM should be recommended in children with complicated ALL to highlight the large individual variability in the responses to 6-MP exposure and the associated adverse effects.

LncRNA Linc-PINT inhibits miR-523-3p to hamper retinoblastoma progression by upregulating Dickkopf-1 (DKK1).

Emerging evidences indicated that long non-coding RNAs (LncRNAs) regulated the pathogenesis of retinoblastoma (RB). However, up until now, the role of LncRNA Linc-PINT in the regulation of RB progression is still largely unknown. The present study identified LncRNA Linc-PINT as a tumor suppressor to hinder RB development by regulating miR-523-3p/Dickkopf-1 (DKK1) axis. Mechanistically, Linc-PINT was low-expressed, while miR-523-3p was high-expressed in RB cells, compared to the normal retinal epithelial cells (ARPE-19). Further gain- and loss-function experiments verified that both upregulation of Linc-PINT and miR-523-3p downregulation slowed down cell growth, invasion and migration, and promoted cell apoptosis in RB cells, but Linc-PINT ablation and miR-523-3p overexpression promoted malignant phenotypes in RB cells. In addition, the dual-luciferase reporter gene system and RNA pull-down assay validated that Linc-PINT positively regulated DKK1 expressions by sponging miR-523-3p, and Linc-PINT inhibited RB progression by regulating miR-523-3p/DKK1 axis. Functionally, we found that both miR-523-3p overexpression and DKK1 silence abrogated the anti-cancer effects of overexpressed Linc-PINT on RB cells. Finally, Linc-PINT inhibited tumorigenicity of RB cells in xenograft mice models. In general, analysis of the data suggested that Linc-PINT inhibited miR-523-3p to upregulate DKK1, resulting in the inhibition of RB, and we demonstrated that Linc-PINT and miR-523-3p could be utilized as potential diagnostic and therapeutic biomarkers for RB in clinic.

Is color source retrieval sensitive to emotion? Electrophysiological evidence from old/new effects.

It has been proved that item memory and source memory are two dissociable processes, as reflected by differential influence at behavioral and electrophysiological levels, the latter being evidenced by the ERP old/new effects. Specially for source memory, the retrieval of color source may be unique from recollecting other types of contextual information, which can be seen from the late posterior negativity (LPN). However, the mediation of emotional valence on the old/new effects for verbal stimuli encoded in colors remains unknown. Adopting words of three emotional valences (i.e., positive, neutral, and negative), with their displayed colors serving as sources, the current experiment aimed to explore the sensitivity of old/new effects to emotion for both item memory and source memory. Results demonstrated that: the FN400 that reflects familiarity was recorded and it was sensitive to emotional valence across both memory tasks; the mediation of emotional valence was absent in recollection-reflected LPC, neither for item memory nor for source memory; an association between LPN and color source retrieval was confirmed, with reliable amplitudes for neutral words but not for emotional words. These data were discussed in terms of the dual-process model and other accounts. Future research directions were recommended.

Drug Elimination Alteration in Acute Lymphoblastic Leukemia Mediated by Renal Transporters and Glomerular Filtration.

PURPOSE: Drug elimination alteration has been well reported in acute lymphoblastic leukemia (ALL). Considering that transporters and glomerular filtration influence, to different extents, the drug disposition, and possible side effects, we evaluated the effects of ALL on major renal transporters and glomerular filtration mediated pharmacokinetic changes, as well as expression of renal drug transporters. METHODS: ALL xenograft models were established and intravenously injected with substrates of renal transporters and glomerular filtration separately in NOD/SCID mice. The plasma concentrations of substrates, after single doses, were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: With the development of ALL, protein expression of MDR1, OAT3 and OCT2 were increased by 2.62-fold, 1.70-fold, and 1.45-fold, respectively, whereas expression of MRP2 and MRP4 were significantly decreased by 30.98% and 45.28% in the kidney of ALL groups compared with control groups. Clearance of MDR1-mediated digoxin, OAT3-mediated furosemide, and OCT2-mediated metformin increased by 3.04-fold, 1.47-fold, and 1.26-fold, respectively. However, clearance of MRPs-mediated methotrexate was reduced by 39.5%. These results are consistent with mRNA expression. Clearance of vancomycin and amikacin, as markers of glomerular filtration rate, had a 2.14 and 1.64-fold increase in ALL mice, respectively. CONCLUSIONS: The specific alteration of renal transporters and glomerular filtration in kidneys provide a rational explanation for changes in pharmacokinetics for ALL.

Sensitivity of Reality Monitoring to Fluency: Evidence from Behavioral Performance and Event-Related Potential (ERP) Old/New Effects.

BACKGROUND Item memory and source memory are differently processed with both behavioral and event-related potential (ERP) evidence. Reality monitoring, a specific type of source memory, which refers to the ability to differentiate external sources from internal sources, has been drawing much attention. Among factors that have an impact on reality monitoring, fluency has not been well-studied. Therefore, the current study aimed to investigate whether fluency could affect reality monitoring, through observations on both behavioral performance and electrophysiological patterns. MATERIAL AND METHODS Adopting ERP techniques, participants were required either to watch the presentation of a name/picture pair, or to imagine a picture for each displayed name, once (low fluency) or twice (high fluency). Later they completed a reality monitoring task of identifying names as perceived, imagined, or novel items. Behavioral performance was measured, and ERP waveforms were recorded. RESULTS Behaviorally, high fluency items were faster and more accurately attributed to the sources than low fluency items. ERP waveforms revealed that late positive component (LPC) occurred for all 4 types of items, while imagined items of low fluency did not record a robust FN400 or late frontal old/new effect. CONCLUSIONS As results revealed, the factor of fluency does influence reality monitoring in terms of accuracy and responding speed. Meanwhile, for imagined items of low fluency, the absence of FN400 and frontal old/new effect also suggests the sensitivity of reality monitoring to fluency, because these representatives of familiarity-based processing and post-retrieval monitoring are inevitably involved in the process of differentiating internal source from external source.

How do word frequency and memory task influence directed forgetting: An ERP study.

In daily life, it is important either to remember sometimes or to intentionally forget on other occasions. The issue of forgetting following instructions (i.e. directed forgetting, DF) has been broadly studied; however, whether the frequency of contents would matter in DF remains unclear, and the understanding of its neural mechanism in both circumstances of item memory and source memory requires improvement in depth. For these purposes, the current study manipulated word frequency and memory task to investigate relevant behavioral features and neural activities of DF. Adopting event-related potential (ERP) technique, this study applied two-character Chinese words of two types of word frequency (high vs low) in the item-method DF paradigm. During encoding, we found that the increased frontal positivity, an index of active inhibition, was regulated by both word frequency and memory task, while the enhanced parietal positivity reflecting selective rehearsal didn't fluctuate across conditions. In the course of test, three ERP old/new effects were identified: the familiarity-based FN400 and the recollection-driven LPC were both modulated by word frequency and memory task, but the right frontal old/new effect was significant solely in source memory; also, these effects provided compelling evidence for the influences of word frequency and memory task on DF. Our results reinforce the differentiation between absolute familiarity and relative familiarity in memory, reveal their sensitivity to DF, and also support the dual-process interpretation. Implications are made to examine more influential factors for future research.

Disrupters as Well as Monitors: Roles of Others During and After Collaborative Remembering in the DRM Procedure.

Influence of others on true and inauthentic memory both during and after collaborative remembering have drawn extensive attention in recent years. Collaborative research has recorded three typical effects: collaborative inhibition and error pruning (i.e., nominal groups recall more true information but also bear higher erroneous intrusions than collaborative groups) during collaboration, as well as post-collaborative recall benefit after collaboration. This study introduced Deese-Roediger-McDermott (DRM) lists not only to investigate these phenomena in semantically related information, but also set a course to explore false memory in the collaborative context. Another issue is the sensitivity of these effects to different episodic memory tests (i.e., item memory and source memory tests). In views of these, the current study instructed participants to study several DRM lists and then recall previously studied words (item recall) together with their displayed colors (source retrieval) twice (Recall 1 and 2). Recall 1 was performed either individually or collaboratively, whereas Recall 2 was conducted individually. The cost of collaborative inhibition was obtained, along with three different beneficial effects: error pruning, false memory reduction, and post-collaborative recall benefit. Furthermore, the novel implication of the current study is that it reveals the sensitivity of collaborative inhibition and error pruning in DRM lists to testing conditions and demonstrates that the modulation of collaboration on false memory occurs in the same way both during and after collaboration. These results are discussed in terms of the retrieval strategy disruption hypothesis and other accounts.