Task-specific relationships between error-related ERPs and behavior: Flanker, Stroop, and Go/Nogo tasks.

Performance monitoring has been widely studied during different forced-choice response tasks. Participants typically show longer response times (RTs) and increased accuracy following errors, but there are inconsistencies regarding the connection between error-related event-related brain potentials (ERPs) and behavior, such as RT and accuracy. The specific task in any given study could contribute to these inconsistencies, as different tasks may require distinct cognitive processes that impact ERP-behavior relationships. The present study sought to determine whether task moderates ERP-behavior relationships and whether these relationships are robustly observed when tasks and stimuli are treated as random effects. ERPs and behavioral indices (RTs and accuracy) recorded during flanker, Stroop, and Go/Nogo tasks from 180 people demonstrated a task-specific effect on ERP-behavior relationships, such that larger previous-trial error-related negativity (ERN) predicted longer RTs and greater likelihood of a correct response on subsequent trials during flanker and Stroop tasks but not during Go/Nogo task. Additionally, larger previous-trial error positivity (Pe) predicted faster RTs and smaller variances of RTs on subsequent trials for Stroop and Go/Nogo tasks but not for flanker task. When tasks and stimuli were treated as random effects, ERP-behavior relationships were not observed. These findings support the need to consider the task used for recording performance monitoring measures when interpreting results across studies.

Yes or no? A study of ErrPs in the "guess what I am thinking" paradigm with stimuli of different visual content.

Error-related potentials (ErrPs) have attracted attention in part because of their practical potential for building brain-computer interface (BCI) paradigms. BCIs, facilitating direct communication between the brain and machines, hold great promise for brain-AI interaction. Therefore, a comprehensive understanding of ErrPs is crucial to ensure reliable BCI outcomes. In this study, we investigated ErrPs in the context of the "guess what I am thinking" paradigm. 23 healthy participants were instructed to imagine an object from a predetermined set, while an algorithm randomly selected another object that was either the same as or different from the imagined object. We recorded and analyzed the participants' EEG activity to capture their mental responses to the algorithm's "predictions". The study identified components distinguishing correct from incorrect responses. It discusses their nature and how they differ from ErrPs extensively studied in other BCI paradigms. We observed pronounced variations in the shape of ErrPs across different stimulus sets, underscoring the significant influence of visual stimulus appearance on ErrP peaks. These findings have implications for designing effective BCI systems, especially considering the less conventional BCI paradigm employed. They emphasize the necessity of accounting for stimulus factors in BCI development.

Pathological personality domains and punishment-enhanced error-related negativity.

The error-related negativity (ERN) is an event-related potential that is observed after the commission of an error and is hypothesized to index threat sensitivity. The ERN is associated with multiple psychiatric disorders, but it is unclear if similar results are due to higher-order dimensions of psychopathology. When errors are punished, the ERN is further enhanced, which might better isolate threat sensitivity. However, few studies have examined whether psychopathology is associated with punishment enhancement of the ERN. In a clinical sample of 170 adults, the present study examined the association between pathological personality domains and predictable vs. unpredictable punishment-enhanced ERN. Results indicated that the ERN was enhanced when errors were punished compared to not punished. Greater negative emotionality was associated with a greater predictable punishment-enhanced ERN, while greater disinhibition was associated with smaller predictable punishment-enhanced ERN. The study suggests that higher-order pathological personality domains demonstrate discriminate relationships with punishment-enhanced error-related brain activity.

Evidence for post-decisional conflict monitoring in delay discounting.

Choice impulsivity can be measured by offering a sequence of various binary choices between smaller, immediately available rewards and larger, later available rewards. An individual's delay discount (DD) rate reflects the aggregate decision-making tendency. Given the broad spectrum of disorders associated with a high DD rate, this may be an important transdiagnostic factor. This study aimed to establish whether post-decisional neurophysiological processes reflecting the presence of error monitoring are involved in delay discounting. A large sample (N = 97) was investigated, including 46 females and 51 males. The electroencephalogram (EEG) was recorded during the classic monetary choice questionnaire (MCQ-27). Error-related event-related potentials (ERPs) and event-related oscillations (EROs) following responses were analyzed. A modest relationship between error positivity (Pe) and DD rate was seen centro-parietal, with higher amplitude for low DD individuals after choosing immediate rewards. A robust association was found between DD rate and theta oscillation power increases. This was most prominent in low DD individuals after making an immediate reward choice. Theta power was positively associated with decision (reaction) time, suggesting an association between pre- and post-decisional conflict. No evidence was found for an error-related negativity (ERN) and delta oscillations. This study provides clear evidence for conflict monitoring as a post-decision process in delay discounting. Findings suggest that diminished theta band power bursts and lower Pe amplitude, observed after choosing an immediate reward, reflect the neurophysiological consequence and possibly the cause of steep delay discounting. High DD was characterized by prefrontal hypoactivation and appears to result from affective decision-making. Highlights.

TXNDC5 Plays a Crucial Role in Regulating Endoplasmic Reticulum Activity through Different ER Stress Signaling Pathways in Hepatic Cells.

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by a number of variables, including endoplasmic reticulum stress (ER). Thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family and acts as an endoplasmic reticulum (ER) chaperone. Nevertheless, the function of TXNDC5 in hepatocytes under ER stress remains largely uncharacterized. In order to identify the role of TXNDC5 in hepatic wild-type (WT) and TXNDC5-deficient (KO) AML12 cell lines, tunicamycin, palmitic acid, and thapsigargin were employed as stressors. Cell viability, mRNA, protein levels, and mRNA splicing were then assayed. The protein expression results of prominent ER stress markers indicated that the ERN1 and EIF2AK3 proteins were downregulated, while the HSPA5 protein was upregulated. Furthermore, the ATF6 protein demonstrated no significant alterations in the absence of TXNDC5 at the protein level. The knockout of TXNDC5 has been demonstrated to increase cellular ROS production and its activity is required to maintain normal mitochondrial function during tunicamycin-induced ER stress. Tunicamycin has been observed to disrupt the protein levels of HSPA5, ERN1, and EIF2AK3 in TXNDC5-deficient cells. However, palmitic acid has been observed to disrupt the protein levels of ATF6, HSPA5, and EIF2AK3. In conclusion, TXNDC5 can selectively activate distinct ER stress pathways via HSPA5, contingent on the origin of ER stress. Conversely, the absence of TXNDC5 can disrupt the EIF2AK3 cascade.

The Role of the European Reference Network for Rare Bone Diseases (ERN BOND) and European Registries for Rare Bone and Mineral Conditions (EuRR-Bone) in the Governance of the Management of Rare Bone and Mineral Diseases.

Rare diseases (RDs) bear a significant challenge to individuals, healthcare systems, and societies. The European reference network on Rare BONe diseases (ERN BOND) is committed to improving multidisciplinary, patient-centred care for individuals with rare bone and mineral diseases (RBMDs). Its affiliated project, the European registries for rare bone and mineral conditions (EuRR-Bone) collects data using two different platforms, an electronic surveillance system (e-REC) that captures the occurrence of RBMDs and the Core Registry, a platform with the infrastructure for collecting Core data fields and longitudinal generic and condition-specific information. With emerging registries and the overlap with other ERNs, it is key to maintain the capability of the platforms to adapt to the needs of the network and the community whilst adhering to quality and FAIR (findable, accessible, interoperable, and reusable) principles. This binomial ensures long-term sustainability and potential advances in the care pathway of RBMDs whilst promoting good practice standards within Europe and beyond.

Reliability Theory for Measurements with Variable Test Length, Illustrated with ERN and Pe Collected in the Flanker Task.

In psychophysiology, an interesting question is how to estimate the reliability of event-related potentials collected by means of the Eriksen Flanker Task or similar tests. A special problem presents itself if the data represent neurological reactions that are associated with some responses (in case of the Flanker Task, responding incorrectly on a trial) but not others (like when providing a correct response), inherently resulting in unequal numbers of observations per subject. The general trend in reliability research here is to use generalizability theory and Bayesian estimation. We show that a new approach based on classical test theory and frequentist estimation can do the job as well and in a simpler way, and even provides additional insight to matters that were unsolved in the generalizability method approach. One of our contributions is the definition of a single, overall reliability coefficient for an entire group of subjects with unequal numbers of observations. Both methods have slightly different objectives. We argue in favor of the classical approach but without rejecting the generalizability approach.

Knockdown of ERN1 disturbs the expression of phosphoserine aminotransferase 1 and related genes in glioblastoma cells.

BACKGROUND: Endoplasmic reticulum stress and synthesis of serine are essential for tumor growth, but the mechanism of their interaction is not clarified yet. The overarching goal of this work was to investigate the impact of ERN1 (endoplasmic reticulum to nucleus signaling 1) inhibition on the expression of serine synthesis genes in U87MG glioblastoma cells concerning the suppression of cell proliferation. METHODS: Wild type U87MG glioblastoma cells and their clones with overexpression of transgenes dnERN1 (without cytoplasmic domain of ERN1) and dnrERN1 (with mutation in endoribonuclease of ERN1), and empty vector (as control) were used. The silencing of ERN1 and XBP1 was also used to inhibition of ERN1 and its function. Gene expression was measured by qPCR. RESULTS: We show that the expression of PSAT1 and several other related to serine synthesis genes is suppressed in cells with ERN1 inhibition by dissimilar mechanisms: PHGDH gene through ERN1 protein kinase, because its expression was resistant to inhibition of ERN1 endoribonuclease, but ATF4 gene via endoribonuclease of ERN1. However, in the control of PSAT1 and PSPH genes both enzymatic activities of ERN1 signaling protein are involved. At the same time, ERN1 knockdown strongly increased SHMT1 expression, which controls serine metabolism and enhances the proliferation and invasiveness of glioma cells. The level of microRNAs, which have binding sites in PSAT1, SHMT1, and PSPH mRNAs, was also changed in cells harboring dnERN1 transgene. Inhibition of ERN1 suppressed cell proliferation and enzymatic activity of PHGDH, a rate-limiting enzyme for serine synthesis. CONCLUSION: Changes in the expression of phosphoserine aminotransferase 1 and other genes related to serine synthesis are mediated by diverse ERN1-dependent mechanisms and contributed to suppressed proliferation and enhanced invasiveness of ERN1 knockdown glioblastoma cell.

Unraveling unmet needs in ketogenic dietary services: An ERN EpiCARE survey.

The implementation and potential of ketogenic dietary therapies (KDTs) have changed over time. The organization of KDT services, the availability of multidisciplinary teams, resources and support for patients and families still vary widely around the world. This diversity is reflected by a lack of consistency in reported outcomes, optimization of using KDT and KDT compliance. To highlight the unmet needs for KDT services, the ERN EpiCARE Ketogenic Dietary Therapy Special Interest Group (KDT SIG) conducted an online survey on KDT implementation and utilization, addressing the following topics: Use and completeness of guidelines and protocols; assessment of compliance and outcome parameters, sustainability and inclusivity in daily life. Consistently reported unmet needs included the lack of psychological support and resources to measure and improve adherence to KDT, the lack of inclusion strategies, and shared guidelines and protocols adapting to specific needs. Future interventions should focus primarily on educational and informative measures together with creation of shared protocols for complex care. PLAIN LANGUAGE SUMMARY: This study provides the results of a survey compiled by clinicians and patients representatives belonging to ERN Epicare, designed to unravel unmet needs from both patients' and healthcare practitioners' perspectives during ketogenic dietary therapies (KDT) provision. Importantly, results show the need to create new shared protocols and guidelines meant for KDT use in complex care situations and to develop future strategies initiatives to support patients improving their social inclusivity.

Error-related brain activity shapes the association between trait neuroticism and internalizing symptomatology in two tasks.

The current study examined how individual differences in error-related brain activity might moderate the association between high trait neuroticism and internalizing symptoms. Data were collected from a sample of high-achieving young adults (N = 188) as part of a larger study on risk versus resiliency for psychopathology. Participants completed two behavioral tasks to elicit the error-related negativity (ERN): an arrow Flanker task and a Go/No-Go task. Analyses were constrained to two internalizing symptom dimensions of checking behavior and irritability. Contrary to expectations, ERN amplitude was not related to symptom severity at the bivariate level. However, ERN amplitude moderated the association between trait neuroticism and symptoms of ill temper, such that the neuroticism-irritability association was strongest among individuals with a blunted ERN. In addition, this finding was relatively consistent across tasks and across two complementary methods of scoring the ERN, suggesting an effect of ERN variance that is shared between tasks and that is relatively robust regarding processing differences. In all, the current study represents the first attempt to investigate how the ERN interacts with trait neuroticism to predict transdiagnostic symptom dimensions in adulthood.

No association between error-related ERPs and trait anxiety in a nonclinical sample: Convergence across analytical methods including mass-univariate statistics.

Enhanced error monitoring, as indexed by increased amplitude of the error-related negativity (ERN) event-related potential (ERP) component, has been suggested to reflect a vulnerability neuro-marker of anxiety disorders. Another error-related ERP component is the error positivity (Pe), which reflects late-stage error processing. The associations between heightened ERN and Pe amplitudes and anxiety levels in the nonclinical population have been inconsistent. In this preregistered study, we examined the association between anxiety, ERN, and Pe, using different analytical methods (mass-univariate analyses, MUAs and conventional analyses), self-reported anxiety scales (STAI and STICSA), and trial numbers (all correct trials and equal numbers of correct and error trials). In a sample of 82 healthy adults, both conventional and MUAs demonstrated a robust enhancement of the ERN and Pe to errors relative to the correct-response ERPs. However, the mass-univariate approach additionally unveiled a wider array of electrodes and a longer effect duration for this error enhancement. Across the analytic methods, the results showed a lack of consistent correlation between trait anxiety and error-related ERPs. Findings were not modulated by trial numbers, analyses, or anxiety scales. The present results suggest a lack of enhancement of error monitoring by anxious traits in individuals with subclinical anxiety and those with clinical anxiety but without a clinical diagnosis. Importantly, the absence of such correlation questions the validity of the ERN as a neural marker for anxiety disorders. Future studies that investigate neuro-markers of anxiety may explore alternative task designs and employ robust statistics to provide a more comprehensive understanding of anxiety vulnerability.

Multiple Adaptive Attention-Bias-Modification Programs to Alter Normative Increase in the Error-Related Negativity in Adolescents.

In the current article, we examined the impact of two home-delivered attentional-bias-modification (ABM) programs on a biomarker of anxiety (i.e., the error-related negativity [ERN]). The ERN is sensitivity to ABM-related changes; however, it is unclear whether ABM exerts its influence on the ERN and anxiety by increasing general attentional control or by disengaging spatial allocation of attention. In this study, we measured the ERN, anxiety, attention bias, and attention control before and after two versions of ABM training and a waitlist control group in 546 adolescents. An ABM designed to increase attention control modulated the ERN but had no impact on anxiety. An ABM designed to reduce attentional bias changed bias and self-reported anxiety in youths but had no impact on the ERN or parent-reported anxiety. These results suggest that the ERN and normative anxiety may be modified using attention training.

Endoplasmic reticulum stress-dependent regulation of the expression of serine hydroxymethyltransferase 2 in glioblastoma cells.

Objective. Serine hydroxymethyltransferase (SHMT2) plays a multifunctional role in mitochondria (folate-dependent tRNA methylation, translation, and thymidylate synthesis). The endoplasmic reticulum stress, hypoxia, and glucose and glutamine supply are significant factors of malignant tumor growth including glioblastoma. Previous studies have shown that the knockdown of the endoplasmic reticulum to nucleus signaling 1 (ERN1) pathway of endoplasmic reticulum stress strongly suppressed glioblastoma cell proliferation and modified the sensitivity of these cells to hypoxia and glucose or glutamine deprivations. The present study aimed to investigate the regulation of the SHMT2 gene in U87MG glioblastoma cells by ERN1 knockdown, hypoxia, and glucose or glutamine deprivations with the intent to reveal the role of ERN1 signaling in sensitivity of this gene expression to hypoxia and nutrient supply. Methods. The control U87MG glioblastoma cells (transfected by an empty vector) and ERN1 knockdown cells with inhibited ERN1 endoribonuclease and protein kinase (dnERN1) or only ERN1 endoribonuclease (dnrERN1) were used. Hypoxia was introduced by dimethyloxalylglycine (500 ng/ml for 4 h). For glucose and glutamine deprivations, cells were exposed in DMEM without glucose and glutamine, respectively for 16 h. RNA was extracted from cells and reverse transcribed. The expression level of the SHMT2 gene was studied by real-time qPCR and normalized to ACTB. Results. It was found that inhibition of ERN1 endoribonuclease and protein kinase in glioblastoma cells led to a down-regulation of SHMT2 gene expression in U87MG cells. At the same time, the expression of this gene did not significantly change in cells with inhibited ERN1 endoribonuclease, but tunicamycin strongly increased its expression. Moreover, the expression of the SHMT2 gene was not affected in U87MG cells after silencing of XBP1. Hypoxia up-regulated the expression level of the SHMT2 gene in both control and ERN1 knockdown U87MG cells. The expression of this gene was significantly up-regulated in glioblastoma cells under glucose and glutamine deprivations and ERN1 knockdown significantly increased the sensitivity of the SHMT2 gene to these nutrient deprivation conditions. Conclusion. The results of the present study demonstrate that the expression of the SHMT2 gene responsible for serine metabolism and formation of folate one-carbon is controlled by ERN1 protein kinase and induced by hypoxia as well as glutamine and glucose deprivation conditions in glioblastoma cells and reflects the ERN1-mediated reprogramming of sensitivity this gene expression to nutrient deprivation.

Inhibition of ERN1 affects the expression of TGIF1 and other homeobox gene expressions in U87MG glioblastoma cells.

BACKGROUND: The ERN1 (endoplasmic reticulum to nucleus signaling 1) pathway plays an important role in the regulation of gene expression in glioblastoma, but molecular mechanism has not yet been fully elucidated. The aim of this study was to evaluate the relative relevance of ERN1 activity as a kinase in comparison to its endoribonuclease activity in the regulation of homeobox gene expression. METHODS: Two sublines of U87MG glioblastoma cells with different ways of ERN1 inhibition were used: dnERN1 (overexpressed transgene without protein kinase and endoribonuclease) and dnrERN1 (overexpressed transgene with mutation in endoribonuclease). ERN1 suppression was also done using siRNA for ERN1. Silencing of XBP1 mRNA by specific siRNA was used for suppression of ERN1 endoribonuclease function mediated by XBP1s. The expression levels of homeobox genes and microRNAs were evaluated by qPCR. RESULTS: The expression of TGIF1 and ZEB2 genes was downregulated in both types of glioblastoma cells with inhibition of ERN1 showing the ERN1 endoribonuclease-dependent mechanism of their regulation. However, the expression of PBX3 and PRPRX1 genes did not change significantly in dnrERN1 glioblastoma cells but was upregulated in dnERN1 cells indicating the dependence of these gene expressions on the ERN1 protein kinase. At the same time, the changes in PAX6 and PBXIP1 gene expressions introduced in glioblastoma cells by dnrERN1 and dnERN1 were different in direction and magnitude indicating the interaction of ERN1 protein kinase and endoribonuclease activities in regulation of these gene expressions. The impact of ERN1 and XBP1 silencing on the expression of studied homeobox genes is similar to that observed in dnERN1 and dnrERN1 glioblastoma cells, correspondingly. CONCLUSION: The expression of TGIF1 and other homeobox genes is dependent on the ern1 signaling pathways by diverse mechanisms because inhibition of ERN1 endoribonuclease and both ERN1 enzymatic activities had dissimilar impacts on the expression of most studied genes showing that ERN1 protein kinase plays an important role in controlling homeobox gene expression associated with glioblastoma cell invasion.

Assessment of gene-disease associations and recommendations for genetic testing for somatic variants in vascular anomalies by VASCERN-VASCA.

BACKGROUND: Vascular anomalies caused by somatic (postzygotic) variants are clinically and genetically heterogeneous diseases with overlapping or distinct entities. The genetic knowledge in this field is rapidly growing, and genetic testing is now part of the diagnostic workup alongside the clinical, radiological and histopathological data. Nonetheless, access to genetic testing is still limited, and there is significant heterogeneity across the approaches used by the diagnostic laboratories, with direct consequences on test sensitivity and accuracy. The clinical utility of genetic testing is expected to increase progressively with improved theragnostics, which will be based on information about the efficacy and safety of the emerging drugs and future molecules. The aim of this study was to make recommendations for optimising and guiding the diagnostic genetic testing for somatic variants in patients with vascular malformations. RESULTS: Physicians and lab specialists from 11 multidisciplinary European centres for vascular anomalies reviewed the genes identified to date as being involved in non-hereditary vascular malformations, evaluated gene-disease associations, and made recommendations about the technical aspects for identification of low-level mosaicism and variant interpretation. A core list of 24 genes were selected based on the current practices in the participating laboratories, the ISSVA classification and the literature. In total 45 gene-phenotype associations were evaluated: 16 were considered definitive, 16 strong, 3 moderate, 7 limited and 3 with no evidence. CONCLUSIONS: This work provides a detailed evidence-based view of the gene-disease associations in the field of vascular malformations caused by somatic variants. Knowing both the gene-phenotype relationships and the strength of the associations greatly help laboratories in data interpretation and eventually in the clinical diagnosis. This study reflects the state of knowledge as of mid-2023 and will be regularly updated on the VASCERN-VASCA website (VASCERN-VASCA, https://vascern.eu/groupe/vascular-anomalies/ ).

Inhibition of signaling protein ERN1 increases the sensitivity of serine synthesis gene expressions to glucose and glutamine deprivations in U87MG glioblastoma cells.

Objective. Glucose and glutamine supply as well as serine synthesis and endoplasmic reticulum (ER) stress are important factors of glioblastoma growth. Previous studies showed that the knockdown of ERN1 (ER to nucleus signaling 1) suppressed glioblastoma cell proliferation and modified the sensitivity of numerous gene expressions to nutrient deprivations. The present study is aimed to investigate the impact of glucose and glutamine deprivations on the expression of serine synthesis genes in U87MG glioblastoma cells in relation to ERN1 knockdown with the intent to reveal the role of ERN1 signaling pathway on the ER stress-dependent regulation of these gene expressions. Clarification of the regulatory mechanisms of serine synthesis is a great significance for glioblastoma therapy. Methods. The control U87MG glioblastoma cells (transfected by empty vector) and ERN1 knockdown cells (transfected by dominant-negative ERN1) were exposed under glucose and glutamine deprivation conditions for 16 h. RNA was extracted from cells and reverse transcribed. The expression level of PHGDH (phosphoglycerate dehydrogenase), PSAT1 (phosphoserine amino-transferase 1), PSPH (phosphoserine phosphatase), ATF4 (activating transcription factor 4), and SHMT1 (serine hydroxymethyltransferase 1) genes was studied by real-time qPCR and normalized to ACTB. Results. It was found that the expression level of genes responsible for serine synthesis such as PHGDH, PSAT1, PSPH, and transcription factor ATF4 was up-regulated in U87MG glioblastoma cells under glucose and glutamine deprivations. Furthermore, inhibition of ERN1 significantly enhances the impact of glucose and especially glutamine deprivations on these gene expressions. At the same time, the expression of the SHMT1 gene, which is responsible for serine conversion to glycine, was down-regulated in both nutrient deprivation conditions with more significant changes in ERN1 knockdown glioblastoma cells. Conclusion. Taken together, the results of present study indicate that the expression of genes responsible for serine synthesis is sensitive to glucose and glutamine deprivations in gene-specific manner and that suppression of ERN1 signaling significantly modifies the impact of both glucose and glutamine deprivations on PHGDH, PSAT1, PSPH, ATF4, and SHMT1 gene expressions and reflects the ERN1-mediated genome reprograming introduced by nutrient deprivation condition.

Performance monitoring and error detection: The role of mid frontal theta and error-related negativity (ERN) among Indian adolescents from different socioeconomic background.

The aim of the study was to investigate the relationship between socioeconomic status (SES) and executive functioning, focusing specifically on performance monitoring, error detection, and their association with mid-frontal theta and error-related negativity (ERN). Employing the widely used flanker task, the research involved two phases with participants aged 10-16 years (15 individuals in the pilot phase and 35 in the second phase). Electroencephalogram (EEG) recordings from distinct brain regions were analyzed during various conditions. The study revealed a notable increase in both absolute and relative theta power at Fcz during the flanker task, with a stronger effect observed during incorrect trials. Furthermore, it underscored the influence of socioeconomic status (SES) on mid-frontal theta, highlighting interactions between SES, gender, and experimental conditions impacting both absolute and relative theta. Intriguingly, the research disclosed a positive correlation between parental occupation and error-related negativity (ERN), as well as between age and ERN. These findings underscore the significance of SES, gender, and age in shaping the neural mechanisms associated with performance monitoring and executive functions. The study contributes valuable insights into the intricate interplay between socio-demographic factors and cognitive processes, shedding light on their impact on goal-directed behaviors and brain activity.

Domain specificity of error monitoring: An ERP study in young and older adults.

Metacognition refers to the ability to monitor and control one's cognitive processes, which plays an important role in decision-making throughout the lifespan. It is still debated whether metacognitive abilities decline with age. Neuroimaging evidence suggests that metacognition is served by domain-specific mechanisms. These domains may differentially decline with increasing age. The current investigates whether the error-related negativity (ERN) and the error positivity (Pe) which reflect error detection and error awareness, respectively, differ across perceptual and memory domains in young and older adults. In total, 38 young adults and 37 older adults completed a classic Flanker Task (perceptual) and an adapted memory-based version. No difference in ERN amplitude was found between young and older adults and across domains. Perceptual ERN peaked earlier than Memory ERN. Memory ΔERN was larger than Perceptual ΔERN. Pe was smaller in older adults and ΔPe was larger for perceptual than memory flanker. Memory Pe peaked earlier in young as compared to older adults. Multivariate analyses of whole scalp data supported cross-domain differences. During the task, ERN decreased in young but not in older adults. Memory Pe decreased in young adults but increased in older adults while no significant change in perceptual Pe was found. The study's findings suggest that neural correlates of error monitoring differ across cognitive domains. Moreover, it was shown that error awareness declines in old age but its within-task dynamics vary across cognitive domains. Possible mechanisms underlying metacognition impairments in aging are discussed.

Genetic diagnosis of endocrine disorders in Cyprus through the Cyprus Institute of Neurology and Genetics: an ENDO-ERN Reference Center.

The report covers the current and past activities of the department Molecular Genetics-Function and Therapy (MGFT) at the Cyprus Institute of Neurology and Genetics (CING), an affiliated Reference Center for the European Reference Network on Rare Endocrine Conditions (Endo-ERN).The presented data is the outcome of > 15 years long standing collaboration between MGFT and endocrine specialists from the local government hospitals and the private sector. Up-to-date > 2000 genetic tests have been performed for the diagnosis of inherited rare endocrine disorders. The major clinical entities included Congenital Adrenal Hyperplasia (CAH) due to pathogenic variants in CYP21A2 gene and Multiple Endocrine Neoplasia (MEN) type 2 due to pathogenic variants in the RET proto-oncogene. Other rare and novel pathogenic variants in ANOS1, WDR11, FGFR1, RNF216, and CHD7 genes were also found in patients with Congenital Hypogonadotropic Hypogonadism. Interestingly, a few patients with Disorders of Sexual Differentiation (DSD) shared rare pathogenic variants in the SRD5A2, HSD17B3 and HSD3B2 while patients with Glucose and Insulin Homeostasis carried theirs in GCK and HNF1A genes. Lastly, MGFT over the last few years has established an esteemed diagnostic and research program on premature puberty with emphasis on the implication of MKRN3 gene on the onset of the disease and the identification of other prognosis biomarkers.As an Endo-ERN member MGFT department belongs to this large European network and holds the same humanistic ideals which aim toward the improvements of health care for patients with rare endocrine conditions in respect to improved and faster diagnosis.

ERN1 knockdown modifies the hypoxic regulation of homeobox gene expression in U87MG glioblastoma cells.

OBJECTIVE.: Homeobox genes play an important role in health and disease including oncogenesis. The present investigation aimed to study ERN1-dependent hypoxic regulation of the expression of genes encoding homeobox proteins MEIS (zinc finger E-box binding homeobox 2) and LIM homeobox 1 family, SPAG4 (sperm associated antigen 4) and NKX3-1 (NK3 homeobox 1) in U87MG glioblastoma cells in response to inhibition of ERN1 (endoplasmic reticulum to nucleus signaling 1) for evaluation of their possible significance in the control of glioblastoma growth. METHODS.: The expression level of homeobox genes was studied in control (transfected by vector) and ERN1 knockdown U87MG glioblastoma cells under hypoxia induced by dimethyloxalylglycine (0.5 mM for 4 h) by quantitative polymerase chain reaction and normalized to ACTB. RESULTS.: It was found that hypoxia down-regulated the expression level of LHX2, LHX6, MEIS2, and NKX3-1 genes but up-regulated the expression level of MEIS1, LHX1, MEIS3, and SPAG4 genes in control glioblastoma cells. At the same time, ERN1 knockdown of glioblastoma cells significantly modified the sensitivity of all studied genes to a hypoxic condition. Thus, ERN1 knockdown of glioblastoma cells removed the effect of hypoxia on the expression of MEIS1 and LHX1 genes, but increased the sensitivity of MEIS2, LHX2, and LHX6 genes to hypoxia. However, the expression of MEIS3, NKX3-1, and SPAG4 genes had decreased sensitivity to hypoxia in ERN1 knockdown glioblastoma cells. Moreover, more pronounced changes under the conditions of ERN1 inhibition were detected for the pro-oncogenic gene SPAG4. CONCLUSION.: The results of the present study demonstrate that hypoxia affected the expression of homeobox genes MEIS1, MEIS2, MEIS3, LHX1, LHX2, LHX6, SPAG4, and NKX3-1 in U87MG glioblastoma cells in gene-specific manner and that the sensitivity of all studied genes to hypoxia condition is mediated by ERN1, the major pathway of the endoplasmic reticulum stress signaling, and possibly contributed to the control of glioblastoma growth. A fundamentally new results of this work is the establishment of the fact regarding the dependence of hypoxic regulation of SPAG4 gene expression on ER stress, in particular ERN1, which is associated with suppression of cell proliferation and tumor growth.