Visual analytics for the interpretation of fluency tests during Alzheimer evaluation

International audienceA possible way to evaluate the progress of Alzheimer disease is to conduct the Isaac set test [13, 14]. In this activity, patients are asked to cite the largest possible number of city names within a minute. Since the city names are handwritten very quickly by a medical practitioner some cities are abbreviated or poorly written. In order to analyze such data, medical practitioners need to digitize the notes first and clean the dataset. Because these tasks are intricate and error prone we propose a novel set of tools, involving interactive visualization techniques, to help medical practitioners in the digitization and data-cleaning process. This system will be tested as part of an ongoing longitudinal study involving 9500 patients

Attentional switch from external toward internal world: a psychophysiological marker

Let’s have an experience. Read the following question and try to answer as sincerely as possible. Meanwhile, observe what’s going on in your mind. Here is the question: “What gift did you receive for Christmas?”. To answer this question, we need to create a temporary internal mental space to which our attention will focus (Tulving, 2002). This attentional switch from external towards internal mental world is commonly referred as mindwandering. Since attention is a limited resource, it cannot focus simultaneously on outside and inside worlds: while our attention is focused on our internal world, we are largely blind to external stimulations (Fernandes & Moscovitch, 2000). There is a perceptual decoupling (Smallwood & Schooler, 2006) which is one of the most threatening aspect of the mindwandering (Schooler et al., 2011)

Le TOP 12 : comment s'en servir pour repérer une pathologie du vieillissement cognitif ?

International audienceIntroduction. Le TOP 12 examine la mémoire collective simplement et rapidement par huit types de question portant sur le souvenir de la vie de 12 célébrités nommément désignées. Objectifs. Vérifier la corrélation entre les scores moyens et le degré de sévérité de la pathologie ; déterminer un seuil permettant de conjecturer sur l'état de la personne au vu de son score au test. Méthodes. L'échantillon est composé de 145 sujets (91 témoins, 32 patients présentant une maladie d'Alzheimer, 21 patients ayant un trouble cognitif léger de type amnésique ou MCIa, 1 patient ayant une démence sémantique). Les propriétés diagnostiques du TOP 12 ont pu être mises en avant en confrontant deux méthodologies : le centilage et la courbe Receiver Operator Characteristic (ROC). Résultats. L'ordre des moyennes et l'ordre des niveaux de gravité pathologique des groupes sont corrélés. Le seuil qui optimise le compromis entre la sensibilité (Se) et la spécificité (Sp) est donné par la méthodologie de la courbe ROC (83 points ; Se = 0,83 ; Sp = 0,70). Le cinquième centile s'avère non optimal étant donné qu'il majore les omissions. Conclusion. Cette validation externe du TOP 12 montre l'intérêt de la méthodologie de la courbe ROC. Mots clés : mémoire collective * TOP 12 * propriétés diagnostiques * centilage * courbe RO

Refining understanding of working memory buffers through the construct of binding:Evidence from a single case informs theory and clinical practice

International audienceBinding operations carried out in working memory enable the integration of information from different sources during online performance. While available evidence suggests that working memory may involve distinct binding functions, whether or not they all involve the episodic buffer as a cognitive substrate remains unclear. Similarly, knowledge about the neural underpinnings of working memory buffers is limited, more specifically regarding the involvement of medial temporal lobe structures. In the present study, we report on the case of patient KA, with developmental amnesia and selective damage to the whole hippocampal system. We found that KA was unable to hold shape-colours associations (relational binding) in working memory. In contrast, he could hold integrated coloured shapes (conjunctive binding) in two different tasks. Otherwise, and as expected, KA was impaired on three relational memory tasks thought to depend on the hippocampus that are widely used in the early detection of Alzheimer's disease. Our results emphasize a dissociation between two binding processes within working memory, suggesting that the visuo-spatial sketchpad could support conjunctive binding, and may rely upon a large cortical network including sub-hippocampal structures. By contrast, we found evidence for a selective impairment of relational binding in working memory when the hippocampal system is compromised, suggesting that the long-term memory deficit observed in amnesic patients may be related to impaired short-term relational binding at encoding. Finally, these findings may inform research on the early detection of Alzheimer's disease as the preservation of conjunctive binding in KA is in sharp contrast with the impaired performance demonstrated very early in this disease

Le TOP 12 : comment interpréter les réponses comme des mesures de la capacité de la mémoire collective ?

International audienceIntroduction. Le TOP 12 évalue la mémoire collective au travers d'une série de huit types de questions portant sur le souvenir de la vie de 12 célébrités nommément désignées. La validation de tels tests est souvent envisagée dans le seul but de prédire un critère externe au test (validation externe) ; la validation interne n'est quant à elle que très rarement étudiée. Objectifs. Montrer comment les réponses obtenues peuvent mesurer une seule grandeur hypothétique (appelée aussi construit) : la capacité de la mémoire collective. Méthodes. L'échantillon est composé de 145 sujets (91 témoins, 32 patients présentant une maladie d'Alzheimer, 21 patients ayant un trouble cognitif léger de type amnésique, 1 patient ayant une démence sémantique). Deux étapes sont nécessaires : modéliser les réponses aux items à l'aide d'un modèle de réponse à l'item à trois paramètres et tester l'unidimensionnalité des scores estimés. Résultats. Les huit modèles s'ajustent étroitement aux données. L'analyse factorielle confirmatoire ne permet pas de rejeter l'idée selon laquelle les huit types de questions mesurent bien une seule et unique grandeur hypothétique. Conclusion. La modélisation psychométrique des données observées avec le TOP 12 indique qu'elles mesurent la capacité de la mémoire collective. Mots clés : mémoire collective * TOP 12 * validation interne * modélisation psychométrique * grandeur hypothétiqu

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Plasticity and cerebral reorganization: an update

International audienc

Implication du cortex périrhinal dans la mémoire de reconnaissance visuelle chez l'homme et diagnostic précoce de la maladie d'Alzheimer

Les dégénérescences neurofibrillaires, responsables de la symptomatologie observée dans la maladie d'Alzheimer, débutent par une sous-région du cortex périrhinal. Cette structure est essentielle pour la réalisation de tâches de mémoire de reconnaissance visuelle chez le singe. Nous faisons l'hypothèse que l'utilisation de ce type de tâche pourrait être utile au diagnostic précoce de la maladie d'Alzheimer. Dans une première partie, nous montrons que le cortex périrhinal a rôle similaire chez l'homme et chez le singe au travers d'approches en neuropsychologie chez le patient cérébrolésé et en électrophysiologie intracérébrale chez le patient épileptique. Dans une deuxième partie, nous présentons deux études montrant que la mémoire de reconnaissance visuelle est altérée, probablement précocement, dans la maladie d'Alzheimer. Nos travaux sont en faveur de nos hypothèses initiales et nous conduisent à développer celle-ciNeurofibrillary tangles, responsible for the early signs of Alzheimer's disease, have been shown to initially appear in a subregion of the perirhinal cortex. In the monkey, damage to the perirhinal cortex severely impairs performance on visual recognition memory tasks. The aim of our thesis was thus to evaluate impairment of visual recognition memory as a potential early diagnostic marker of AD. Using neuropsychology in brain lesioned patients and intracerebral electrophysiology in patients with epilepsy, we first conducted a series of study, which show that the perirhinal cortex is a critical region for visual recognition memory in humans as it is in the monkey. We present in a second section two studies that show that visual recognition memory is impaired, probably early, in Alzheimer's disease. Our studies support our initial hypothesis and lead us to reformulate it in the light of our recent findingsAIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Improving the integrative memory model by integrating the temporal dynamics of memory

International audienceDespite highlighting the role of the attribution system and proposing a coherent large-scale architecture of declarative memory, the integrative memory model would be more "integrative" if the temporal dynamics of the interactions between its components was clarified. This is necessary to make predictions in patients with brain injury and hypothesize dissociations