Interoceptive and metacognitive facets of fatigue in multiple sclerosis

Numerous disorders are characterised by fatigue as a highly disabling symptom. Fatigue plays a particularly important clinical role in multiple sclerosis (MS) where it exerts a profound impact on quality of life. Recent concepts of fatigue grounded in computational theories of brain-body interactions emphasise the role of interoception and metacognition in the pathogenesis of fatigue. So far, however, for MS, empirical data on interoception and metacognition are scarce. This study examined interoception and (exteroceptive) metacognition in a sample of 71 persons with a diagnosis of MS. Interoception was assessed by prespecified subscales of a standard questionnaire (Multidimensional Assessment of Interoceptive Awareness [MAIA]), while metacognition was investigated with computational models of choice and confidence data from a visual discrimination paradigm. Additionally, autonomic function was examined by several physiological measurements. Several hypotheses were tested based on a preregistered analysis plan. In brief, we found the predicted association of interoceptive awareness with fatigue (but not with exteroceptive metacognition) and an association of autonomic function with exteroceptive metacognition (but not with fatigue). Furthermore, machine learning (elastic net regression) showed that individual fatigue scores could be predicted out-of-sample from our measurements, with questionnaire-based measures of interoceptive awareness and sleep quality as key predictors. Our results support theoretical concepts of interoception as an important factor for fatigue and demonstrate the general feasibility of predicting individual levels of fatigue from simple questionnaire-based measures of interoception and sleep

Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment

Juvenile myelomonocytic leukemia (JMML) is a rare aggressive myelodysplastic/myeloproliferative neoplasm of early childhood, initiated by RAS-activating mutations. Genomic analyses have recently described JMML mutational landscape; however, the nature of JMML-propagating cells (JMML-PCs) and the clonal architecture of the disease remained until now elusive. Combining genomic (exome, RNA-seq), Colony forming assay and xenograft studies, we detect the presence of JMML-PCs that faithfully reproduce JMML features including the complex/nonlinear organization of dominant/minor clones, both at diagnosis and relapse. Further integrated analysis also reveals that although the mutations are acquired in hematopoietic stem cells, JMML-PCs are not always restricted to this compartment, highlighting the heterogeneity of the disease during the initiation steps. We show that the hematopoietic stem/progenitor cell phenotype is globally maintained in JMML despite overexpression of CD90/THY-1 in a subset of patients. This study shed new lights into the ontogeny of JMML, and the identity of JMML-PCs, and provides robust models to monitor the disease and test novel therapeutic approaches

The Confidence Database

Understanding how people rate their confidence is critical for the characterization of a wide range of perceptual, memory, motor and cognitive processes. To enable the continued exploration of these processes, we created a large database of confidence studies spanning a broad set of paradigms, participant populations and fields of study. The data from each study are structured in a common, easy-to-use format that can be easily imported and analysed using multiple software packages. Each dataset is accompanied by an explanation regarding the nature of the collected data. At the time of publication, the Confidence Database (which is available at https://osf.io/s46pr/) contained 145 datasets with data from more than 8,700 participants and almost 4 million trials. The database will remain open for new submissions indefinitely and is expected to continue to grow. Here we show the usefulness of this large collection of datasets in four different analyses that provide precise estimations of several foundational confidence-related effects

Intégration des croyances et valeurs affectives dans la prise de décision chez l'homme

Executive control relates to the human ability to monitor and flexibly adapt behavior in relation to internal mental states. Specifically, executive control relies on evaluating action outcomes for adjusting subsequent action. Actions can be reinforced or devaluated given affective value of outcomes, notably in basal ganglia and medial prefrontal cortex. Additionally, outcomes convey information to adapt behavior in relation to internal beliefs, involving prefrontal cortex. Accordingly, action outcomes convey two major types of value signals: (1) Affective values, representing the valuation of action outcomes given subjective preferences and stemming from reinforcement learning; (2) Belief values about how actions map onto outcome contingencies and relating to Bayesian inference. However, how these two signals contribute to decision remains unclear, and previous experimental paradigms confounded them. In this PhD thesis, we investigated whether their dissociation is behaviorally and neurally relevant. We present several behavioral experiments dissociating these two signals, in the form of probabilistic reversal-learning tasks involving stochastic and changing reward structures. We built a model establishing the functional and computational foundations of such dissociation. It combined two parallel systems: reinforcement learning, modulating affective values, and Bayesian inference, monitoring beliefs. The model accounted for behavior better than many other alternative models. We then investigated whether beliefs and affective values have distinct neural bases using fMRI. BOLD signal was regressed against choice-dependent and choice-independent beliefs and affective values. Ventromedial prefrontal cortex (VMPFC) and midcingulate cortex (MCC) activity correlated with both choice-dependent variables. However, we found a double-dissociation regarding choice-independent variables, with VMPFC encoding choice-independent beliefs, whereas MCC encoded choice-independent affective values. Additionally, activity in lateral prefrontal cortex (LPFC) increased when decision values (i.e. mixture of beliefs and affective values) got closer to each other and action selection became more difficult. These results suggest that before decision, VMPFC and MCC separately encode beliefs and affective values respectively. LPFC combines both signals to decide, then feeds back choice information to these medial regions, presumably for updating these value signals according to action outcomes. These results provide new insight into the neural mechanisms of decision-making in prefrontal cortex.Le contrôle exécutif de l'action fait référence a la capacité de l'homme a contrôler et adapter son comportement de manière flexible, en lien avec ses états mentaux internes. Il repose sur l’évaluation des conséquences des actions pour ajuster les choix futurs. Les actions peuvent être renforcées ou dévalues en fonction de la valeur affective des conséquences, impliquant notamment les ganglions de la base et le cortex préfrontal médian. En outre, les conséquences des actions portent une information, qui permet d'ajuster le comportement en relation avec des croyances internes, impliquant le cortex préfrontal. Ainsi, les conséquences des actions portent deux types de signaux : (1) Une valeur affective, qui représente l’évaluation de la conséquence de l'action selon les préférences subjectives, issue de l'apprentissage par renforcement ; (2) Une valeur de croyance, mesurant comment les actions correspondent aux contingences externes, en lien avec l’inférence bayésienne. Cependant, la contribution de ces deux signaux a la prise de décision reste méconnue. Dans cette these, nous avons étudie la pertinence de cette dissociation aux niveaux comportemental et cérébral. Nous présentons plusieurs expériences comportementales permettant de dissocier ces deux signaux de valeur, sous la forme de taches d'apprentissage probabiliste avec des structures de récompense stochastiques et changeantes. Nous avons construit un modelé établissant les fondations fonctionnelles et computationnelles de la dissociation. Il combine deux systèmes en parallèle : un système d'apprentissage par renforcement modulant les valeurs affectives, et un système d’inférence bayésienne modulant les croyances. Le modèle explique mieux le comportement que de nombreux modèles alternatifs. Nous avons ensuite étudie, en IRM fonctionnelle, si les représentations dépendantes et indépendantes du choix des croyances et des valeurs affectives avaient des bases neurales distinctes. L’activité du cortex préfrontal ventromédian (VMPFC) et du cortex mid-cingulaire (MCC) corrélé avec les deux variables dépendantes du choix. Cependant, une double-dissociation a été identifiée concernant les représentations indépendantes du choix, le VMPFC étant spécifique des croyances alors que le MCC est spécifique des valeurs affectives. En outre, l’activité du cortex préfrontal latéral augmente lorsque les deux valeurs de décision sont proches et que le choix devient difficile. Ces résultats suggèrent qu'avant la décision, le cortex préfrontal ventromédian (VMPFC) et le cortex mid-cingulaire (MCC) encodent séparément les croyances et les valeurs affectives respectivement. Le cortex préfrontal latéral (LPFC) combine les deux signaux pour prendre une décision, puis renvoie l'information du choix aux régions médianes, probablement pour actualiser les deux signaux de valeur en fonction des conséquences du choix. Ces résultats contribuent a élucider les mécanismes cérébraux de la prise de décision dans le cortex préfrontal

Vers une pédagogie de l'uniformisation des dispensations de traitements antiretroviraux

PARIS-BIUP (751062107) / SudocSudocFranceF

A shared brain system forming confidence judgment across cognitive domains

International audienceConfidence is typically defined as a subjective judgment about whether a decision is right. Decisions are based on sources of information that come from various cognitive domains and are processed in different brain systems. An unsettled question is whether the brain computes confidence in a similar manner whatever the domain or in a manner that would be idiosyncratic to each domain. To address this issue, human participants performed two tasks probing confidence in decisions made about the same material (history and geography statements), but based on different cognitive processes: semantic memory for deciding whether the statement was true or false, and duration perception for deciding whether the statement display was long or short. At the behavioral level, we found that the same factors (difficulty, accuracy, response time, and confidence in the preceding decision) predicted confidence judgments in both tasks. At the neural level, we observed using functional magnetic resonance imaging that confidence judgments in both tasks were associated to activity in the same brain regions: positively in the ventromedial prefrontal cortex and negatively in a prefronto-parietal network. Together, these findings suggest the existence of a shared brain system that generates confidence judgments in a similar manner across cognitive domains

Prefrontal mechanisms combining rewards and beliefs in human decision-making

Optimal decision-making requires integrating expectations about rewards with beliefs about reward contingencies. Here, the authors show that these aspects of reward are encoded in the ventromedial prefrontal cortex then combined in the dorsomedial prefrontal cortex, a process that guides choice biases characteristic of human decision-making

Du domicile à l’institution : évolution des réseaux de sociabilité

International audienceSociological research on the sociability of older people has been relatively abundant since the early 2000s, although the perspective for the analysis of personal networks (Bidart, Degenne, Grossetti, 2011) in connection with a study on social support bringing these links together is much less common. The aim of this article is to explore and characterize the evolution of the network of personal relationships of older adults on the basis of a retrospective narrative analysis, in other words, before and after their admission to a nursing home. The reflection suggested here is based on an empirical method to gather data on sixteen research interviews with older people currently living in nursing homes. The results of the study show the heuristic nature of this network-like approach and the various restructurings of the “small world” or social surroundings of older people once they have been admitted to a nursing institution.Les recherches sociologiques sur la sociabilité des vieilles personnes sont relativement abondantes depuis le début des années 2000, en revanche la perspective d’analyse en termes de dynamique des réseaux de relations personnelles (Bidart, Degenne et Grossetti, 2011), couplée à l’étude du soutien social circulant à travers les liens, est beaucoup moins fréquente. Le présent article a pour objet d’explorer et de caractériser l’évolution des réseaux de relations de personnes vieillissantes selon une procédure narrative rétrospective, c’est-à-dire avant et après leur entrée en établissement d’hébergement pour personnes âgées. La réflexion proposée ici s’appuie sur un matériau empirique récolté dans le cadre de seize entretiens de recherche menés auprès de vieilles personnes vivant actuellement dans des lieux d’hébergement pour personnes âgées. Les résultats de recherche montrent l’intérêt heuristique de cette « approche réseau » et les diverses restructurations qui affectent le « petit monde » ou l’entourage social des individus vieillissants une fois entrés en institution

A shared brain system forming confidence judgment across cognitive domains

Abstract Confidence is typically defined as a subjective judgment about whether a decision is right. Decisions are based on sources of information that come from various cognitive domains and are processed in different brain systems. An unsettled question is whether the brain computes confidence in a similar manner whatever the domain or in a manner that would be idiosyncratic to each domain. To address this issue, human participants performed two tasks probing confidence in decisions made about the same material (history and geography statements), but based on different cognitive processes: semantic memory for deciding whether the statement was true or false, and duration perception for deciding whether the statement display was long or short. At the behavioral level, we found that the same factors (difficulty, accuracy, response time, and confidence in the preceding decision) predicted confidence judgments in both tasks. At the neural level, we observed using functional magnetic resonance imaging that confidence judgments in both tasks were associated to activity in the same brain regions: positively in the ventromedial prefrontal cortex and negatively in a prefronto-parietal network. Together, these findings suggest the existence of a shared brain system that generates confidence judgments in a similar manner across cognitive domains.</p