Positive Feedback Research Articles

The Principle of Cortical Development and Evolution.

Human's robust cognitive abilities, including creativity and language, are made possible, at least in large part, by evolutionary changes made to the cerebral cortex. This paper reviews the biology and evolution of mammalian cortical radial glial cells (primary neural stem cells) and introduces the concept that a genetically step wise process, based on a core molecular pathway already in use, is the evolutionary process that has molded cortical neurogenesis. The core mechanism, which has been identified in our recent studies, is the extracellular signal-regulated kinase (ERK)-bone morphogenic protein 7 (BMP7)-GLI3 repressor form (GLI3R)-sonic hedgehog (SHH) positive feedback loop. Additionally, I propose that the molecular basis for cortical evolutionary dwarfism, exemplified by the lissencephalic mouse which originated from a larger gyrencephalic ancestor, is an increase in SHH signaling in radial glia, that antagonizes ERK-BMP7 signaling. Finally, I propose that: (1) SHH signaling is not a key regulator of primate cortical expansion and folding; (2) human cortical radial glial cells do not generate neocortical interneurons; (3) human-specific genes may not be essential for most cortical expansion. I hope this review assists colleagues in the field, guiding research to address gaps in our understanding of cortical development and evolution.

Inactivated cGAS-STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2- Breast Cancer.

Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.

New therapeutics for the prevention or amelioration of fetal alcohol spectrum disorders: a narrative review of the preclinical literature.

Background: Ethanol consumption during pregnancy induces enduring detrimental effects in the offspring, manifesting as a spectrum of symptoms collectively termed as Fetal Alcohol Spectrum Disorders (FASD). Presently, there is a scarcity of treatments for FASD.Objectives: To analyze current literature, emphasizing evidence derived from preclinical models, that could potentially inform therapeutic interventions for FASD.Methods: A narrative review was conducted focusing on four prospective treatments: nutritional supplements, antioxidants, anti-inflammatory compounds and environmental enrichment. The review also highlights innovative therapeutic strategies applied during early (e.g. folate administration, postnatal days 4-9) or late (e.g. NOX2 inhibitors given after weaning) postnatal stages that resulted in significant improvements in behavioral responses during adolescence (a critical period marked by the emergence of mental health issues in humans).Results: Our findings underscore the value of treatments centered around nutritional supplementation or environmental enrichment, aimed at mitigating oxidative stress and inflammation, implying shared mechanisms in FASD pathogenesis. Moreover, the review spotlights emerging evidence pertaining to the involvement of novel molecular components with potential pharmacological targets (such as NOX2, MCP1/CCR2, PPARJ, and PDE1).Conclusions: Preclinical studies have identified oxidative imbalance and neuroinflammation as relevant pathological mechanisms induced by prenatal ethanol exposure. The relevance of these mechanisms, which exhibit positive feedback loop mechanisms, appear to peak during early development and decreases in adulthood. These findings provide a framework for the future development of therapeutic avenues in the development of specific clinical treatments for FASD.

Intron Retention of DDX39A Driven by SNRPD2 is a Crucial Splicing Axis for Oncogenic MYC/Spliceosome Program in Hepatocellular Carcinoma.

RNA splicing is a dynamic molecular process in response to environmental stimuli and is strictly regulated by the spliceosome. Sm proteins, constituents of the spliceosome, are key components that mediate splicing reactions; however, their potential role in hepatocellular carcinoma (HCC) is poorly understood. In the study, SNRPD2 (PD2) is found to be the most highly upregulated Sm protein in HCC and to act as an oncogene. PD2 modulates DDX39A intron retention together with HNRNPL to sustain the DDX39A short variant (39A_S) expression. Mechanistically, 39A_S can mediate MYC mRNA nuclear export to maintain high MYC protein expression, while MYC in turn potentiates PD2 transcription. Importantly, digitoxin can directly interact with PD2 and has a notable cancer-suppressive effect on HCC. The study reveals a novel mechanism by which DDX39A senses oncogenic MYC signaling and undergoes splicing via PD2 to form a positive feedback loop in HCC, which can be targeted by digitoxin.

New Scenarios for Training in Oral Radiology: Clinical Performance and Predoctoral Students' Perception of 3D-Printed Mannequins.

This study aimed to evaluate the impact of 3D-printed mannequins on the training of predoctoral students. Two 3D-printed training models were developed: a traditional model that simulates a sound adult patient and a customized model with pathological and physiological changes (impacted third molar and edentulous region). Students accomplished their pre-clinical training divided into a control group (CG, n = 23), which had access to the traditional model, and a test group (TG, n = 20), which had access to both models. Afterward, they performed a full mouth series on patients and filled out a perception questionnaire. Radiographs were evaluated for technical parameters. Descriptive statistics and the Mann-Whitney test were used to compare the groups. Students provided positive feedback regarding the use of 3D printing. The TG reported a more realistic training experience than the CG (p = 0.037). Both groups demonstrated good clinical performance (CG = 7.41; TG = 7.52), and no significant differences were observed between them. 3D printing is an option for producing simulators for pre-clinical training in Oral Radiology, reducing student stress and increasing confidence during clinical care.

Delay characteristics of quasi-nonvolatile memory devices operating in positive feedback mechanism.

This study examines the memory and read delay characteristics of quasi-nonvolatile memory (QNVM) devices operating in a positive feedback mechanism through technology computer-aided design simulation. The QNVM devices exhibit a rapid operation speed of 5 ns, a significant sensing margin of approximately 8.0 μA, and a retention time of around 1 s without any external bias. These devices showcase an exceptionally brief read delay of 0.12 ns. The energy band diagrams during the memory operation are analysed to clarify the factors influencing the read delay. The write and standby conditions modulate the potential barrier height during the standby operation, thereby affecting the read delay. Moreover, the shorter rising time causes the reduction of the read delay. This study demonstrates that the QNVM device has the potential to resolve energy consumption and speed issues in nonvolatile memory devices.

A modular inquiry-based semester theme that integrates data science education and bioinformatics in protein structure function courses.

With an exponential growth in biological data and computing power, familiarity with bioinformatics has become a demanding and popular skill set both in academia and industry. There is a need to increase students' competencies to be able to take on bioinformatic careers, to get them familiarized with scientific professions in data science and the academic training required to pursue them, in a field where demand outweighs the supply. Here we implemented a set of bioinformatic activities into a protein structure and function course of a graduate program. Concisely, students were given hands-on opportunities to explore the bioinformatics-based analyses of biomolecular data and structural biology via a semester-long case study structured as inquiry-based bioinformatics exercises. Towards the end of the term, the students also designed and presented an assignment project that allowed them to document the unknown protein that they identified using bioinformatic knowledge during the term. The post-module survey responses and students' performances in the lab module imply that it furthered an in-depth knowledge of bioinformatics. Despite having not much prior knowledge of bioinformatics prior to taking this module students indicated positive feedback. The students got familiar with cross-indexed databases that interlink important data about proteins, enzymes as well as genes. The essential skillsets honed by this research-based bioinformatic pedagogical approach will empower students to be able to leverage this knowledge for their future endeavours in the bioinformatics field.

Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates β-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-β signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.

4D transperineal ultrasound: feedback for good obstetric anal sphincter injuries reparation.

Obstetric anal injury is the main risk factor for traumatic anal, faecal and flatus, incontinence in women in reproductive age. Its recognition and good reparation are crucial for long term outcomes. We report a case of a nulliparous woman who reported a fourth-degree perineal tear after delivery. The obstetric anal sphincter injury was repaired and a four-dimensional transperineal ultrasound was performed after reparation and then one and three months after discharge. The woman did not experience any incontinence and no points of discontinuity were observed at tomographic ultrasound imaging reconstruction. In this case, 4D-TPUS was a tool in the obstetrician's hands to evaluate the surgical success of OASIS repair, which requires some expertise. 4D-TPUS ultrasound is useful and reliable during immediate puerperium and in the subsequent follow-up, giving positive feedback on the correct positioning of the stiches and on a good healing process. Further studies are needed to demonstrate this usefulness in the operators training and for improving their surgical skills.

Electronic oral health surveillance system for Egyptian preschoolers using District Health Information System (DHIS2): design description and time motion study

BackgroundEarly childhood caries (ECC) is a major global health issue affecting millions of children. Mitigating this problem requires up-to-date information from reliable surveillance systems. This enables evidence-based decision-making to devise oral health policies. The World Health Organization (WHO) advocates the adoption of mobile technologies in oral disease surveillance because of their efficiency and ease of application. The study describes developing an electronic, oral health surveillance system (EOHSS) for preschoolers in Egypt, using the District Health Information System (DHIS2) open-source platform along with its Android App, and assesses its feasibility in data acquisition.MethodsThe DHIS2 Server was configured for the DHIS2 Tracker Android Capture App to allow individual-level data entry. The EOHSS indicators were selected in line with the WHO Action Plan 2030. Two modalities for the EOHSS were developed based on clinical data capture: face-to-face and tele/asynchronous. Eight dentists in the pilot team collected 214 events using modality-specific electronic devices. The pilot’s team's feedback was obtained regarding the EOHSS's feasibility in collecting data, and a time-motion study was conducted to assess workflow over two weeks. Independent t-test and Statistical Process Control techniques were used for data analysis.ResultsThe pilot team reported positive feedback on the structure of the EOHSS. Workflow adaptations were made to prioritize surveillance tasks by collecting data from caregivers before acquiring clinical data from children to improve work efficiency. A shorter data capture time was required during face-to-face modality (4.2 ± 0.7 min) compared to telemodality (5.1 ± 0.9 min), p < 0.001). The acquisition of clinical data accounted for 16.9% and 21.1% of the time needed for both modalities, respectively. The time required by the face-to-face modality showed random variation, and the tele-modality tasks showed a reduced time trend to perform tasks.ConclusionsThe DHIS2 provides a feasible solution for developing electronic, oral health surveillance systems. The one-minute difference in data capture time in telemodality compared to face-to-face indicates that despite being slightly more time-consuming, telemodality still shows promise for remote oral health assessments that is particularly valuable in areas with limited access to dental professionals, potentially expanding the reach of oral health screening programs.

Single-cell transcriptomics analysis of bullous pemphigoid unveils immune-stromal crosstalk in type 2 inflammatory disease

Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand–receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.

Intracellular domain of epithelial cell adhesion molecule induces Wnt receptor transcription to promote colorectal cancer progression

BackgroundEpithelial cell adhesion molecule (EpCAM) has been widely studied as a tumor antigen due to its expression in varieties of solid tumors. Moreover, the glycoprotein contributes to critical cancer-associated cellular functionalities via its extracellular (EpEX) and intracellular (EpICD) domains. In colorectal cancer (CRC), EpCAM has been implicated in the Wnt signaling pathway, as EpICD and β-Catenin are coordinately translocated to the nucleus. Once in the nucleus, EpICD transcriptionally regulates EpCAM target genes that; however, remains unclear whether Wnt signaling is modulated by EpICD activity.MethodsPatient-derived organoids (PDOs), patient-derived xenografts (PDXs), and various CRC cell lines were used to study the roles of EpCAM and EpICD in Wnt receptor expression. Fluorescence and confocal microscopy were used to analyze tumors isolated from PDX and other xenograft models as well as CRC cell lines. EpCAM signaling was intervened with our humanized form of EpCAM neutralizing antibody, hEpAb2-6. Wnt receptor promoters under luciferase reporters were constructed to examine the effects of EpICD. Luciferase reporter assays were performed to evaluate promoter, γ-secretase and Wnt activity. Functional assays including in vivo tumor formation, organoid formation, spheroid and colony formation experiments were performed to study Wnt related phenomena. The therapeutic potential of EpCAM suppression by hEpAb2-6 was evaluated in xenograft and orthotopic models of human CRC.ResultsEpICD interacted with the promoters of Wnt receptors (FZD6 and LRP5/6) thus upregulated their transcriptional activity inducing Wnt signaling. Furthermore, activation of Wnt-pathway-associated kinases in the β-Catenin destruction complex (GSK3β and CK1) induced γ-secretase activity to augment EpICD shedding, establishing a positive-feedback loop. Our hEpAb2-6 antibody blocked EpICD-mediated upregulation of Wnt receptor expressions and conferred therapeutic benefits in both PDX and orthotopic models of human CRC.ConclusionsThis study uncovers relevant functions of EpCAM where Wnt receptors are upregulated via the transcriptional co-factor activity of EpICD. The resultant enhancement of Wnt signaling induces γ-secretase activity further stimulating EpICD cleavage and its nuclear translocation. Our humanized anti-EpCAM antibody hEpAb2-6 blocks these mechanisms and may thereby provide therapeutic benefit in CRC.

Resource gain or resource pain? How managerial social support resources influence the impact of sales anxiety on burnout

There is growing recognition that many salespeople frequently experience anxiety, which may impact salesperson mental health and well-being. Unfortunately, there is little empirical evidence on how to manage this situation. Using a longitudinal sample of 156 business-to-business salespeople, the present study examines the impact of sales anxiety on the key mental health outcome of burnout, alongside providing recommendations to sales managers on how to manage this impact. The results suggest that sales anxiety is positively related to each individual component of burnout, and that positive supervisor feedback plays a mitigating role in each of these relationships. By contrast, however, a social climate of autonomy can strengthen the impact of sales anxiety on emotional exhaustion and depersonalization. The present study contributes to the developing literature on salesperson mental health, further advancing emerging evidence that autonomy can result in detrimental outcomes. Implications, limitations, and future research avenues are discussed.

Supporting graduate students’ skills with simulated experiences in a professional foundation course

The population’s health depends on a well-educated nursing workforce that includes graduate-prepared nurses. However, the nation’s demand for graduate nurses in advanced practice, teaching, and research roles surpasses the supply. Graduate nursing educators can support student success by creating positive learning experiences for students at the beginning of their study programs. Initially, we created a pilot writing orientation, which was implemented for new students. Although the results of the pilot study showed significance with paired t-tests (p &lt; .000; Cohen’s d = 1.21), the writing skills were not applied in long-term coursework. Therefore, a seven-week course was created to provide students with small-scale assignments, preparing them for complex future graduate coursework. The study aimed to evaluate the effectiveness of the skills learned in the course using student (n = 15) and faculty (n = 9) focus groups. A qualitative design using thematic analysis showed the following student themes: tools to improve scholarly writing, magnitude and feasibility of the project, graduate-level writing and professional presentations, clear expectations of achieving program requirements, and professional development using a digital e-portfolio. Faculty focus groups compared the skills of students who had completed the course and those who had not. Faculty themes included stronger writing skills despite the variation, resource availability, tool use, APA format skills, and writing synthesis skills development. Overall, the participants’ perspectives shared positive feedback with insightful suggestions for future course improvement.

TGF-β1-Induced LINC01094 promotes epithelial-mesenchymal transition in hepatocellular carcinoma through the miR-122-5p/TGFBR2-SAMD2-SMAD3 Axis.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. It has been proven that long non-coding RNAs (lncRNAs) play an essential role in regulating HCC progression. However, the involvement of LINC01094 in regulating epithelial-mesenchymal transition (EMT) in HCC remains unclear. LINC01094 expression in HCC patients was retrieved from the Cancer Genome Atlas database. Overexpressing and downregulating LINC01094 were conducted to investigate its biological functions using Hep3B, SNU-387, and HuH-7 cells. Western blotting and morphological observation were performed to study the EMT in HCC cells. Transwell assay was adopted to determine the migration and invasion of HCC cells. The underlying mechanism of competitive endogenous RNAs (ceRNAs) was investigated using bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction, and rescue experiments. Elevated LINC01094 expression was observed in HCC and associated with a poor prognosis. Knockdown of LINC01094 expression in SNU-387 and HuH-7 cells could inhibit migration, invasion, and EMT markers. Overexpression of LINC01094 indicated that LINC01094 promoted EMT via the TGF-β/SMAD signaling pathway. The bioinformatics analysis revealed that miR-122-5p was a target of LINC01094. The miRWalk database analysis showed that TGFBR2, SMAD2, and SMAD3 were downstream targets of miR-122-5p. Mechanically, LINC01094 acted as a ceRNA that facilitated HCC metastasis by sponging miR-122-5p to regulate the expression of TGFBR2, SMAD2, and SMAD3. Further, TGF-β1 could enhance the expression of LINC01094, forming a positive feedback loop. TGF-β1-induced LINC01094 expression promotes HCC cell migration and invasion by targeting the miR-122-5p/TGFBR2-SMAD2-SMAD3 axis. LINC01094 may be a potential prognostic biomarker and therapeutic target for HCC metastasis.

REDD1 knockdown ameliorates endothelial cell senescence through repressing TXNIP-mediated oxidative stress

Endothelial cell senescence characterized by reactive oxygen species (ROS) accumulation and chronic inflammation is widely recognized as a key contributor to atherosclerosis (AS). Regulated in development and DNA damage response 1 (REDD1), a conserved stress-response protein that regulates ROS production, is involved in the pathogenesis of various age-related diseases. However, the role of REDD1 in endothelial cell senescence is still unclear. Here, we screened REDD1 as a differentially expressed senescence-related gene in the AS progression using bioinformatics methods, and validated the upregulation of REDD1 expression in AS plaques, senescent endothelial cells, and aging aorta by constructing AS mice, D-galactose (DG)-induced senescent endothelial cells and DG-induced accelerated aging mice, respectively. siRNA against REDD1 could improve DG-induced premature senescence of endothelial cells and inhibit ROS accumulation, similar to antioxidant N-Acetylcysteine (NAC) treatment. Meanwhile, NAC reduced the upregulation of REDD1 induced by DG, supporting the positive feedback loop between REDD1 and ROS contributes to endothelial cell senescence. Mechanistically, the regulatory effect of REDD1 on ROS might be related to the TXNIP-REDD1 interaction in DG-induced endothelial cell senescence. Collectively, experiments above provide evidence that REDD1 participates in endothelial cell senescence through repressing TXNIP-mediated oxidative stress, which may be involved in the progression of atherosclerosis.

Monitoring of surgical staff x-ray exposure in the operating room with DosiBadge

Surgical procedures involving the use of x-rays in the operating room (OR) have increased in recent years, thereby increasing the exposure of OR staff to ionizing radiation. An individual dosimeter makes it possible to record the radiation exposure to which these personnel are exposed, but there is a lack of compliance in the wearing of these dosimeters for several practical reasons. This makes the dose results obtained unreliable. To try to improve the rate of dosimeter wearing in the OR, the Dosibadge project studied the association of the individual dosimeter with the hospital access badge, forming the Dosibadge. Through a study performed at the Tours University Hospital in eight different ORs for two consecutive periods of 3 months. The results show a significant increase in the systematic use of the dosimeter thanks to the Dosibadge, which improves the reliability of the doses obtained on the dosimeters and the monitoring of personnel. The increase is especially marked with clinicians. Following these results and the very positive feedback to this first single-centre study, we are then planning a second multicentre study to validate our proof of concept on different sites, with the three brands of individual dosimeters used in France i.e. dosimeters supplied by Dosilab; Landauer and IRSN.

Supporting victim-survivors during investigations of health practitioner misconduct: early learnings from a trauma-informed service

ObjectiveIn 2021, the Australian Health Practitioner Regulation Agency established a support service to provide additional assistance to victim-survivors involved in complaints related to sexual boundary violations. This study evaluates the...

Spontaneous molecular bromine production in sea salt aerosols.

Bromine chemistry is responsible for the catalytic ozone destruction in the atmosphere. The heterogeneous reactions of sea-salt aerosols are the main abiotic sources of reactive bromine in the atmosphere. Here, we present a novel mechanism for the activation of bromide ions (Br-) by O2 and H2O in the absence of additional oxidants. The laboratory and theoretical calculation results demonstrated that under dark conditions, Br-, O2 and H3O+ could spontaneously generate Br and HO2 radicals through a proton-electron transfer process at the air‒water interface and in the liquid phase. Our results also showed that light and acidity could significantly promote the activation of Br- and the production of Br2. The estimated gaseous Br2 production rate under light conditions was up to 1.55×1010 molecules·cm-2·s-1 under light and acidic conditions; these results showed a significant contribution to the atmospheric reactive bromine budget. The reactive oxygen species (ROS) generated during Br- activation could promote the multiphase oxidation of SO2 to produce sulfuric acid, while the increase in acidity had a positive feedback effect on Br- activation. Our findings highlight the crucial role of the proton-electron transfer process in Br2 production.

Subjective cognitive decline in healthy older adults is associated with altered processing of negative versus positive feedback in a probabilistic learning task

Older adults who worry about their own cognitive capabilities declining, but who do not show evidence of actual cognitive decline in neuropsychological tests, are at an increased risk of being diagnosed with dementia at a later time. Since neural markers may be more sensitive to early stages of cognitive decline, in the present study we examined whether event-related potential responses of feedback processing, elicited in a probabilistic learning task, differ between healthy older adults recruited from the community, who either did (subjective cognitive decline/SCD-group) or did not report (No-SCD group) worry about their own cognition declining beyond the normal age-related development. In the absence of group differences in learning from emotionally charged feedback in the probabilistic learning task, the amplitude of the feedback-related negativity (FRN) varied with feedback valence differently in the two groups: In the No-SCD group, the FRN was larger for positive than negative feedback, while in the SCD group, FRN amplitude did not differ between positive and negative feedback. The P3b was enhanced for negative feedback in both groups, and group differences in P3b amplitude were not significant. Altered sensitivity in neural processing of negative versus positive feedback may be a marker of SCD.