Error Negativity Does Not Reflect Conflict: A Reappraisal of Conflict Monitoring and Anterior Cingulate Cortex Activity

Our ability to detect and correct errors is essential for our adaptive behavior. The conflict-loop theory states that the anterior cingulate cortex (ACC) plays a key role in detecting the need to increase control through conflict monitoring. Such monitoring is assumed to manifest itself in an electroencephalographic (EEG) component, the "error negativity" (Ne or "error-related negativity" [ERN]). We have directly tested the hypothesis that the ACC monitors conflict through simulation and experimental studies. Both the simulated and EEG traces were sorted, on a trial-by-trial basis, as a function of the degree of conflict, measured as the temporal overlap between incorrect and correct response activations. The simulations clearly show that conflict increases as temporal overlap between response activation increases, whereas the experimental results demonstrate that the amplitude of the Ne decreases as temporal overlap increases, suggesting that the ACC does not monitor conflict. At a functional level, the results show that the duration of the Ne depends on the time needed to correct (partial) errors, revealing an "on-line" modulation of control on a very short time scale

Independent component analysis reveals the unity of cognitive control

ISBN : 978-2-9532965-0-1In reaction time tasks, when subjects commit an error, a negative wave peaking approximatively 70-100ms after the erroneous response is recorded with EEG. This negativity, called "Error (Related) Negativity" (Ne or ERN[1, 2]), is maximal fronto-centrally, above the anterior cingulate cortex and/or SMA and was first interpreted as reflecting an error detection mechanism. However, after Laplacian estimation, a similar component was later observed on correct trials [3]. If this component on correct trials were to be the same as the one observed on errors, this would put important constraints on computational models of cognitive control. To address this issue we used Independent Com- ponent Analysis (ICA) to evaluate whether a single component (in ICA terms) could account for the waves observed in both erroneous and correct trials. For all the participants, a single component that accounts for the waves observed in the three categories of trials was found. The localisation of the sources is consistent with a rostral-cingulate zone origin, where control mechanisms are likely implemented [4]. This novel use of ICA allowed us to conclude that the negativities observed on error and correct trials are reflecting the same physiological mechanism whose amplitude is modulated as function of the performance

Fréquence des anémies sévères chez les enfants âgés de 2 mois à 15 ans au Centre Mère et Enfant de la Fondation Chantal Biya, Yaoundé, Cameroun

Introduction: Les anémies sévères constituent une cause importante de décès d’enfants. Une analyse épidémiologique et clinique permettrait d’estimer la morbidité et mortalité y relatives afin lutter efficacement contre les causes. Méthodes: Notre étude rétrospective et descriptive porte sur les anémies sévères chez les enfants de 2 mois à 15 ans de juillet 2005 à juillet 2011. Les drépanocytaires et les enfants souffrant de néoplasie étaient exclus. Toutes les admissions de janvier 2008 à juillet 2011 et les décès totaux, qui répondaient aux critères ci-dessus ont été également répertoriés. Résultats: Ont été analysés 4735 cas d’anémie sévère dont 215 décès (4,5%). Entre janvier 2008 et juillet 2011, sur 12879 enfants hospitalisés 2456 souffraient d’anémie sévère dont 96 sont décédés, soit une mortalité spécifique de 0,7% et une létalité de 4,0%. Au total, 22,4% d’anémies sévères survenaient dans la tranche d’âge de moins de 12 mois. Celles de 12 à 59 mois et de plus de 5 ans représentaient respectivement 64,4% et 13,2% des cas. Le paludisme était l’étiologie évoquée chez 89,0% des cas, suivi du sepsis (9,4%). Les décès concernaient les enfants sévèrement anémiés âgés de 12 à 59 mois dans 67,2% de cas. La plupart de patients (84,8%) résidaient à Yaoundé (P = 0,004). Conclusion: Les anémies sévères restent fréquentes à Yaoundé. La mise en oeuvre de da politique de gratuité des antipaludiques et l’utilisation des moustiquaires doivent être effectives. Le renforcement de ces mesures dès le début des saisons pluvieuses préviendrait les flambées d’anémies.Pan African Medical Journal 2012; 12:4

Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake.

Melanin-Concentrating Hormone (MCH) is one of the most relevant orexigenic factors specifically located in the lateral hypothalamic area (LHA), with its physiological relevance demonstrated in studies using several genetically manipulated mice models. However, the central mechanisms controlling MCH-induced hyperphagia remain largely uncharacterized. Here, we show that central injection of MCH in mice deficient for kappa opoid receptor (k-OR) failed to stimulate feeding. To determine the hypothalamic area responsible for this MCH/k-OR interaction, we performed virogenetic studies and found that downregulation of k-OR by adeno-associated viruses (shOprk1-AAV) in LHA, but not in other hypothalamic nuclei, was sufficient to block MCH-induced food intake. Next, we sought to investigate the molecular signaling pathway within the LHA that mediates acute central MCH stimulation of food intake. We found that MCH activates k-OR and that increased levels of phosphorylated extracellular signal regulated kinase (ERK) are associated with downregulation of phospho-S6 Ribosomal Protein. This effect was prevented when a pharmacological inhibitor of k-OR was co-administered with MCH. Finally, the specific activation of the direct upstream regulator of S6 (p70S6K) in the LHA attenuated MCH-stimulated food consumption. Our results reveal that lateral hypothalamic k-OR system modulates the orexigenic action of MCH via the p70S6K/S6 pathway

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Supervision de l'action et optimisation des comportements : Etudes électrophysiologiques et IRMf

We studied the cerebral mechanisms involved in the optimisation of performance. In order to increase the knowledge of these mechanisms, we ran EEG and fMRI experiments in reaction time task in which we manipulated the stimulus-response compatibility. Firstly, we investigated the role of the negativity of error (Ne), an EEG component which has been discovered in errors and which reaches its maximum just after the response. The Ne was first interpreted as reflecting the error detection. We suggest that the Ne, localised in the rostral cingulate zone, is involved in the evaluation of the performance in order to correct erroneous responses. Secondly, we were interested in mechanisms involved in response selection. The N-40, recorded over the supplementary motor area, is proposed to play a role in the response selection stage. Error prevention would take place at the primary motor cortices level by an enhancement of the response threshold when necessary. Thirdly, we showed, in a fMRI study, that the behavioural adjustment after an incompatible trial is due to an increase of the processing of relevant feature of the stimulus and an decrease of the irrelevant one. In this work, we clarified the role of the Ne and the processes which are responsible for the behavioural adjustments. These results suggest the existence of mechanism able to detect on-line the error risk involved in preventing errors.Les mécanismes cérébraux impliqués dans l'optimisation des comportements sont encore mal connus. Nous avons cherché à préciser leurs fonctionnement à travers des études EEG et IRMf dans des tâches de temps de réaction manipulant la compatibilité Stimulus-Réponse. Plusieurs arguments issus de méthodologies différentes nous ont permis de préciser le rôle de la Négativité d'Erreur (Ne), une onde EEG initialement rapportée dans les erreur, et qui atteint son maximum juste après la réponse. Initialement attribuée à la détection de l'erreur, cette activité, localisée dans la zone cingulaire rostrale, pourrait avoir pour rôle d'évaluer la performance en cours d'essai dans le but de rattraper l'erreur. Nous nous sommes intéressés aux mécanismes impliqués de la sélection de la réponse. La N-40, enregistrée au dessus de l'aire motrice supplémentaire, incarnerait l'association stimulus-réponse alors que les cortex moteurs seraient le lieu de la mise en place d'un mécanisme de prévention de l'erreur implémenté par une élévation du seuil de déclenchement des réponses en présence d'un risque d'erreur. Enfin dans une étude IRMf, nous avons montré que les ajustements comportementaux suite à un essai incompatible prenaient la forme d'une augmentation du traitement perceptif des caractéristiques pertinentes de la tâche et d'une diminution du traitement des caractéristiques non-pertinentes. Nous avons précisé le rôle fonctionnel de la \Ne ainsi que les opérations mises en jeu lors de la mise en place des ajustements comportementaux. Ces résultats suggèrent également l'existence de mécanismes capables de détecter en ligne un risque d'erreur dans le but de prévenir une erreur en cours d'essai

Becoming a Mother During COVID-19: Adjustments in Performing Motherhood

Based on online semi-structured interviews with middle-class women who were pregnant or had recently given birth in Western Europe (France, Spain, the United Kingdom, and Switzerland), this study analyses how motherhood has been experienced and performed during the COVID-19 pandemic. The article reflects on the specific new risk assessments and responsibilities that emerged during the pandemic by showing women’s coping strategies concerning lockdowns and other public health measures. Using a COVID-19 lens also allows a broader analysis of middle-class families’ concerns about performing ‘good motherhood’. By highlighting the discrepancies between women’s expected and actual experiences, the prescriptive aspects of pregnancy, delivery, and the postpartum phase are revealed and analysed, prompting us to consider parenting as a form of doing and proving. By underlining the importance attached to the expectant mother’s wellbeing, the partner’s involvement, the support of relatives, and the future socialisation of the baby, we argue that women face a myriad of imperatives to ensure a meaningful experience of motherhood

Efficient but less mobilized monitoring system in individuals with high aggressive predispositions

Aggressive behaviors in pathological and healthy populations have been largely related to poor cognitive control functioning. However, few studies investigated the influence of aggressive traits (i.e., aggressiveness) on cognitive control. In the current study, we investigated the effects of aggressiveness on cognitive control abilities and particularly, on performance monitoring. Thirty-two participants performed a Simon task while electroencephalography (EEG) and electromyography (EMG) were recorded. Participants were classified as high and low aggressive using the BPAQ questionnaire (Buss &amp; Perry, 1992). EMG recordings were used to reveal three response types by uncovering small incorrect muscular activations in ~15% of correct trials (i.e., partial-errors) that have to be distinguished from full-error and pure-correct responses. For these three response types, EEG recordings were used to extract fronto-central negativities indicative of performance monitoring, the error and correct (-related) negativities (ERN/Ne and CRN/Nc). Behavioral results indicated that the high aggressiveness group had a larger congruency effect compared to the low aggressiveness group, but there were no differences in accuracy. EEG results revealed a global reduction in performance-related negativities amplitudes in all the response types in the high aggressiveness group compared to the low aggressiveness group. Interestingly, the distinction between the ERN/Ne and the CRN/Nc components was preserved both in high and low aggressiveness groups. In sum, high aggressive traits did not affect the capacity to self-evaluate erroneous from correct actions but are associated with a decrease in the importance given to one’s own performance. The implication of these findings are discussed in relation to pathological aggressiveness