While previous research on episodic memory vividness aims at measuring episodic memory, such cognitive tasks also involve visual mental imagery since vividness is primarily a property of visual mental imagery. Literature also shows that subjective measurements of visual mental imagery (e.g., the Vividness of Visual Imagery Questionnaire; VVIQ) are confounded by demand characteristic effects, either by participant response biases or instructional cues. Investigating such claims is most suitable in those who report an absence of visual mental imagery, that is, in aphantasia. Therefore, this study examines whether subjective vividness ratings are interpreted differently between a “visualize” and a “recollect” version of the VVIQ. One hundred and thirty-nine participants filled out online either one of the versions of the questionnaire, which also included an additional manipulation on demand characteristics (i.e., instructional cues on what alleged previous research found on response patterns). Eighty-nine participants self-described with aphantasia. Results showed that irrespective of self-describing with aphantasia or not, participants scored comparably on the two versions of the questionnaire (with aphantasic participants scoring overall lower than control participants), favouring the interpretation that episodic memory vividness involves visual mental imagery. Furthermore, no demand characteristic effects were found in those self-describing with aphantasia, whereas controls’ questionnaire scores were affected only negatively by the employed instructional cues. Different interpretations of such results are discussed, highlighting the idea that it is a difficult methodological exercise to discern the two theoretical constructs: visual mental imagery and episodic memory.

Episodic memory refers to the storage and retrieval of information about events in our past. According to dual process models, episodic memory is supported by familiarity which refers to the rapid and automatic sense of oldness about a previously encoded stimulus, and recollection which refers to the retrieval of contextual information, such as spatial, temporal or other contextual details that bring a specific item to mind. To be clear, familiarity is traditionally assumed to support recognition of item information, whereas recollection supports the recognition of associative information. Event Related Potential (ERP) studies provide support for dual process models, by demonstrating qualitatively distinct patterns of neural activity associated with familiarity (Mid-Frontal old/new effect) and recollection (Left-Parietal old/new effect). In the current thesis, ERPs were used to address two important questions regarding associative recognition – namely, the function of the neural signal supporting recollection and whether familiarity can contribute to the retrieval of novel associative information. The first series of experiments was aimed at addressing how recollection operates by employing a recently developed continuous source task designed to directly measure the accuracy of retrieval success. To date, the function of recollection has been fiercely debated, with some arguing that recollection reflects the operation of a continuous retrieval process, whereby test cues always elicit some information from memory. Alternatively, recollection may reflect the operation of a thresholded process that allows for retrieval failure, whereby test cues sometimes elicit no information from memory at all. In the current thesis, the Left Parietal effect was found to be sensitive to the precision of memory responses when recollection succeeded, but was entirely absent when recollection failed. The result clarifies the nature of the neural mechanism underlying successful retrieval whilst also providing novel evidence in support of threshold models of recollection. The second series of experiments addressed whether familiarity could contribute to the retrieval of novel associative information. Recent associative recognition studies have suggested that unitization (whereby multi-component stimuli are encoded as a single item rather than as a set of associated parts) can improve episodic memory by increasing the availability of familiarity during retrieval. To date, however, ERP studies have failed to provide any evidence of unitization for novel associations, whereas behavioural support for unitization is heavily reliant on model specific measures such as ROC analysis. Over three separate associative recognition studies employing unrelated word pairs, the magnitude of the Mid-Frontal old/new effect was found to be modulated by encoding instructions designed to manipulate the level of unitization. Importantly, the results also suggest that different encoding strategies designed to manipulate the level of unitization may be more successful than others. Finally, the results also revealed that differences in behavioural performance and modulation of the Mid-Frontal old/new effect between unitized and non-unitized instructions is greater for unrelated compared to related word pairs. In essence, the results suggest that unitization is better suited to learning completely novel associations as opposed to word pairs sharing a pre-existing conceptual relationship. Overall, the data presented in this thesis supports dual process accounts of episodic memory, suggesting that at a neural level of analysis, recollection is both thresholded and variable, whilst also supporting the assumption that familiarity can contribute to successful retrieval of novel associative information. The results have important implications for our current understanding of cognitive decline and the development of behavioural interventions aimed at alleviating associative deficits.

réalisé en co-tutelle avec l'Université François-Rabelais de Tours / L’objectif général de cette thèse était de tester l’efficacité d’un entraînement exécutif ainsi que de tester les transferts des bénéfices de cet entraînement sur d’autres fonctions cognitives notamment la mémoire épisodique au niveau comportemental et électrophysiologique chez des adultes âgés. Pour cela, des effets test-retest ont été observés lors de la passation d’un même test de façon consécutive. Ainsi, la création de nouveaux tests pour confectionner le programme d’entraînement a été nécessaire pour ne pas avoir ces effets tests re-tests lors de la passation des pré-tests et des post-tests. Les entraînements exécutifs ont permis l’amélioration du fonctionnement exécutif mais aussi l’amélioration de la vitesse de traitement, et ces bénéfices ont permis l’annulation des effets d’âge dans le groupe entraîné sur une fonction exécutive : la mise à jour de la mémoire de travail. De plus, des effets de transfert ont été obtenus sur l’utilisation stratégique lors de l’encodage d’information en mémoire épisodique. Plus précisément, les adultes âgés entraînés utilisaient plus de stratégies d’encodages efficaces (encodage profond de type imagerie mentale ou phrase) après l’entraînement exécutif et l’utilisation de ces stratégies était plus efficace. Au niveau cérébral, l’entraînement exécutif semble engendrer des processus de spécialisation cérébrale se traduisant par une diminution de l’activité cérébrale de certaines zones cérébrales. Ce travail de thèse incite le développement de programmes d’entraînement des fonctions exécutives qui semblent permettre des effets de transfert à des tâches non entraînées et ces bénéfices semblent aussi modifier le fonctionnement cérébral, ce qui suppose un effet plus durable. Ceci confirme l’idée qu’un environnement stimulant cognitivement est en lien avec de bonnes capacités cognitives et contribue à un vieillissement réussi. / The main objective of this thesis was to test the efficiency of an executive training program and the transfer effects of this program on other cognitive functions, in particular episodic memory strategies and performance. The present work was based on behavioral and electrophysiological data. Practice effects of executive tests have been first tested in young and older adults. Two tests have been practiced across ten practice sessions, and the results showed that the executive functions scores increased after practice, more for the older adults than for the younger ones. In order to develop an executive training program requiring several different tests, we have created new executive tests. The psychometric validity of these tests has been verified and confirmed. These tests have been used for our executive program. Thus, if training effects appeared following this program, they will not be due to the practice of a unique test. Eight sessions of executive stimulation with our new tests have allowed older adults increasing their executive functioning, measured by tests which were different from those employed in the training program (near transfer effects). Other cognitive functions were also improved, as processing speed and episodic memory. For the first time in the literature, far transfer effect have been found memory strategy efficiency and memory performance. More especially, the older adults trained group used more efficient memory strategies (mental imagery or making sentence with the words to be learnt) after the executive training program, and these strategies were more efficient to recall the words. Thus, the memory performance was increased in this group, in comparison the older adults group who did not participate to the training program. At a cerebral level, the executive training seems to decrease the duration of the cerebral activity for the same memory task. However, these results must to be taken with caution and require further analyses to be interpreted correctly. The results of this thesis encourages the development of training programs for executive functions which allows the transfer effects to untrained tasks. These benefits also appear to modify the brain functioning, which implies a longer lasting benefit effect. This work supports the idea that a cognitively stimulating environment is in line with higher cognitive abilities and contributes to successful aging

This thesis employed an integrated approach and investigated intra- and inter-individual differences relevant for normally hearing (NH) and hearing-impaired (HI) adults in native (Swedish) and non-native (English) languages in adverse listening conditions. The integrated approach encompassed the role of cognition as a focal point of interest as well as perceptualauditory and linguistic factors. Paper I examined the extent to which proficiency in a non-native language influenced native and non-native speech perception performance for NH listeners in noise maskers compared to native and non-native speech maskers. Working memory capacity in native and non-native languages and non-verbal intelligence were also assessed. The design of paper II was identical to that of paper I, however the participants in paper II had a hearingimpairment. The purpose of paper III was to assess how NH and HI listeners subjectively evaluated the perceived disturbance from the speech- and noise maskers in the native and nonnative languages. Paper IV examined how well native and non-native stories that were presented unmasked and masked with native and non-native speech were recalled by NH listeners. Paper IV further investigated the role of working memory capacity in the episodic long-term memory of story contents as well as proficiency in native and non-native languages. The results showed that generally, the speech maskers affected performance and perceived disturbance more than the noise maskers did. Regarding the non-native target language, interference from speech maskers in the dominant native language is taxing for speech perception performance, perceived disturbance and memory processes. However, large inter- individual variability between the listeners was observed. Part of this variability relates to non-native language proficiency. Perceptual and cognitive effort may hinder efficient long-term memory encoding, even when stimuli are appropriately identified at a perceptual level. A large working memory capacity (WMC) provides a better ability to suppress distractions and allocate processing resources to meet assigned objectives. The relatively large inter-individual differences in this thesis, require an individualized approach in clinical or educational settings when non-native persons or people with hearing impairment need to perceive and remember potentially vital information. Individua  differences in the very complex process of speech understanding and recall need to be further addressed by future studies. The relevance of cognitive factors and language proficiency provides opportunities for individuals who face difficulties to compensate using other abilities. / Avhandlingens övergripande syfte var att genom ett integrerat tillvägagångssätt undersöka mellan- och inom-individuella skillnader relevanta för normalhörande och hörselskadade vuxna i svenska och engelska språket under ogynnsamma lyssningsförhållanden. Med kognitiva faktorer i fokus, omfattade det integrerade tillvägagångssättet också perceptuella-auditiva och lingvistiska faktorer. Studie I undersökte i vilken utsträckning färdigheter i engelska inverkade på taluppfattning av ett modersmål och ett andra språk som var maskerat med brus jämfört med störande tal på svenska och engelska. Normalhörande vuxna deltog. Arbetsminneskapacitet på svenska och engelska liksom icke-verbal intelligens bedömdes också i studien. Designen i studie II var identisk med designen i studie I, förutom att personer med hörselnedsättning ingick som deltagare. Syftet med studie III var att bedöma hur normalhörande personer och personer med hörselnedsättning subjektivt utvärderade den upplevda störningen från tal- och brus på ett modersmål och ett andra språk. Studie IV undersökte hur väl normalhörande deltagare kom ihåg berättelser på svenska och engelska som presenterades omaskerade eller med störande tal på svenska eller engelska. Studie IV undersökte vidare  arbetsminneskapacitet och episodiskt långtidsminne av berättelsernas innehåll liksom också färdighet i svenska och engelska språket. Resultaten visade att generellt var maskeringseffekten större vid störande tal jämfört med andra bruskällor både vad avser taluppfattning såväl som upplevd störning. Vad det gäller det engelska språket som talsignal, är störning från det svenska modersmålet påfrestande för taluppfattning, upplevd störning såväl som för minnesprocesser. Dock har stor inter- och intra-individuell variation mellan deltagarna observerats. En del av denna variation avser engelska språkfärdigheter. Perceptuell och kognitiv påfrestning kan minska möjligheten till att säkra långsiktiga minnesprocesser även om ett stimuli var korrekt identifierat på en perceptuell nivå. En god arbetsminneskapacitet kan ge en bättre förmåga att undertrycka en distraktion och därmed fördela processresurserna för att nå de uppställda målen. De relativt stora inter-individuella skillnaderna i denna avhandling gör det angeläget med en individualiserad  tillämpning, kliniskt eller inom utbildningsmässiga områden när personer med hörselnedsättning eller personer med ett annat modersmål behöver uppfatta eller minnas potentiellt viktig information. De individuella skillnader som ligger bakom taluppfattning och minnesförmåga behöver utforskas vidare. Goda kognitiva förmågor och språkfärdigheter ger möjligheter för individer som möter svårigheter till att kompensera genom att använda dessa förmågor.

Within this thesis the role of cognitive processes in irritable bowel syndrome (IBS) will be examined. A systematic review and meta-analysis of the rate of psychiatric comorbidity in IBS participants, relative to controls, was performed. Evidence supported heightened rates of psychiatric disorder. A novel hypothesis regarding overlapping cognitive vulnerability to IBS and psychiatric disorders was found to fit well with the pattern of comorbidity. Competing hypotheses and the potential moderators were examined. Overall, no single model of psychiatric morbidity in IBS could fully account for the results of the meta-analysis. The implications of this meta-analysis for a cognitive approach to IBS are discussed. Cognitive processes were directly investigated in two experiments. First, in a modified exogenous cueing task, which assessed attention to pain words, there was faster orienting towards, and engagement with pain words in IBS participants relative to controls. Next, participants completed a primed lexical decision task, which indexed interpretation biases by measuring response times to targets after ambiguous illness primes. Relative to controls, IBS participants’ responses were slower to target words presented after ambiguous illness primes, and demonstrated priming for targets related to the neutral meaning of the illness prime. In the second study, different IBS and healthy control participants completed an internet-based survey of autobiographical memory. Participants described and rated painful and emotional autobiographical events. IBS participants reported pain memories from a more observer perspective relative to controls, suggesting a possible coping strategy for pain content. Finally, three cognitive styles, alexithymia, rumination and self-blame, were evaluated using existing and novel self-report measures. Overall, when compared with healthy participants, IBS participants reported: less difficulty identifying feelings as indexed by the alexithymia measure; increased pain-focused rumination; and a general, negative self-blame. These results may imply a vigilance-avoidance model of cognitive processing in IBS.

Il a été suggéré que lorsqu’une trace de mémoire consolidée est rappelée (réactivée), elle devient instable et sujette aux modifications avant de se stabiliser à nouveau en mémoire à long terme. Nous avons récemment démontré que lorsque la réactivation d’un souvenir négatif est couplée à l’exposition à un stress psychosocial, le souvenir de l’évènement négatif est augmenté de façon durable. En se basant sur ces résultats, le but de cette thèse est de préciser le rôle du stress psychologique et physiologique (hormones de stress) sur la modulation de souvenirs réactivés. Plus précisément, la première étude visait à déterminer si le cortisol, hormone de stress majeure, est un joueur clé dans la modulation des souvenirs réactivés. Pour ce faire, nous avons inhibé pharmacologiquement les niveaux de cortisol au moment de la réactivation d’un souvenir contenant des segments neutres et négatifs. Les résultats démontrent que la réactivation du matériel négatif est amoindrie lorsque les niveaux de cortisol sont inhibés, et cet effet est toujours présent quatre jours plus tard. Étant donné que les stimuli utilisés jusqu’à maintenant ont une faible validité écologique, nous avons voulu déterminer si d’autres types de mémoires pouvaient également être modulables lors de leur réactivation. L’objectif de la deuxième étude était donc de déterminer si les mémoires autobiographiques collectives sont modulables par le stress au moment de leur réactivation. Pour ce faire, nous avons exposé les participants à de vrais extraits de journaux, neutres ou négatifs, afin de réactiver les mémoires collectives associées à ces évènements. Par la suite, tous les participants ont été exposés à un stress psychosocial et leur mémoire des extraits a été évaluée la journée suivante. Les résultats démontrent que les femmes ayant lu les nouvelles négatives avaient une réactivité physiologique accrue face au stresseur et une mémoire augmentée de ces mêmes nouvelles le jour suivant. Ce phénomène n’était cependant pas observable chez les hommes. Le but de la troisième étude était de déterminer si les mémoires autobiographiques personnelles sont modulables par le stress au moment de leur réactivation. Nous avons demandé aux participants de se remémorer deux évènements de leur passé, négatifs ou neutres. Par la suite, ils ont été exposés à un stress psychosocial et leur mémoire pour ces mêmes évènements a été évaluée à nouveau la journée suivante. Les résultats démontrent que les mémoires autobiographiques personnelles réactivées ne semblent pas être modulables par l’exposition à un stresseur. Globalement, les résultats de cette thèse démontrent que le cortisol a la capacité de moduler des souvenirs négatifs réactivés, mais que la nature (extrinsèque vs. intrinsèque) et l'intensité des souvenirs réactivés sont des facteurs déterminants pour que ce phénomène prenne place. / It has been suggested that when a consolidated memory trace is recalled (reactivated), it becomes active and sensitive to modifications before stabilizing again in the long-term memory system. We have recently demonstrated that when the reactivation of a negative memory is followed by exposition to a psychosocial stressor, the memory for the negative material is enhanced in a long-lasting manner. Based on these results, the goal of this thesis is to clarify the role of physiological (stress hormones) and psychological stress on the modulation of reactivated memories. More precisely, the first study aimed to determine whether cortisol, a major stress hormone, is a key player in the modulation of reactivated memories. To do so, we have pharmacologically inhibited cortisol levels at the time of reactivating a memory composed of neutral and negative segments. Results showed that the reactivation of the negative material is decreased when cortisol levels are inhibited and this effect is still present four days later. Given that the stimuli used so far have a weak ecological validity, we wanted to determine whether other types of memories could also be modified upon their reactivation. The goal of the second study was to examine whether collective autobiographical memories were sensitive to the effects of stress at the time of reactivation. To do so, we have exposed participants to real newspaper excerpts, either neutral or negative, in order to reactivate the collective memories associated to these events. We have then exposed all the participants to a psychosocial stressor and their memory for the excerpts was assessed the following day. Results showed that women who have read negative news excerpts had a more pronounced physiological reactivity to the stressor and an increased memory for these news the following day. This phenomenon, however, was not observed in men. The goal of the third study was to determine whether personal autobiographical memories were sensitive to the effects of stress at the time of their reactivation. We have asked participants to recall two personal events, either negative or neutral. We then exposed them to a stressor and their memory for these events was tested the following day. The results showed that reactivated personal autobiographical memories were not sensitive to stress. Globally, the results of this thesis show that cortisol has the capacity to modulate reactivated negative memories, but that the nature (extrinsic vs. intrinsic) and the intensity of the memories are determining factors for this phenomenon to occur.

Ces dernières années, la prise en compte des difficultés quotidiennes des personnes a largement évolué pour être aujourd’hui au centre des préoccupations des cliniciens et chercheurs. Dans le vieillissement en particulier, les difficultés quotidiennes tiennent une place particulière car elles constituent un critère de diagnostic de la démence mais également un facteur de risque de celle-ci, même en l’absence de trouble cognitif avéré.Leur prise en compte relève donc d’un intérêt majeur mais pose la question de leur mesure, notamment au vu des relations non systématiques qu’elles entretiennent avec les troubles cognitifs évalués par les tests neuropsychologiques traditionnels et les plaintes des sujets. Les approches écologiques, la réalité virtuelle en particulier, dans lesquelles s’inscrivent nos travaux, tentent de proposer une évaluation de la cognition « quotidienne » en espérant par ce bais, fournir des mesures qui soient à la fois précises, spécifiques et reflétant le fonctionnement quotidien de la personne. L’utilisation de deux environnements virtuels, représentant un appartement et un quartier résidentiel nous a permis de dégager des profils cognitifs spécifiques associés au vieillissement normal et à la maladie d’Alzheimer dans le cadre de la mémoire épisodique et de navigation spatiale. Ces profils sont discutés en référence au modèle multifactoriel du vieillissement et au regard de l’objectivation des difficultés quotidiennes des personnes. L’application de ces recherches pour le développement d’aides à l’autonomie des âgés est proposé comme perspective de travail. / These last years, taking account of everyday difficulties has largely improved and is at the core of preoccupations of clinicians and researchers.Particularly, everyday difficulties hold a special place in aging because of their potential value as a diagnostic criterion, but also as a risk factor, for dementia, even in the absence of cognitive impairment. However, despite being taken into consideration and their major interest, their assessment is being questioned, especially regarding their inconsistent relationships with cognitive impairments assessed by traditional neuropsychological tests and subjects’ complaints. The purpose of ecological approaches, particularly those using virtual reality technologies, in which our work is framed, is to assess the “daily” cognition, by which we hope providing measures that are accurate, specific and reflecting the one’s daily functioning. The use of two virtual environments, an apartment and a residential district, has allowed us identifying specific cognitive patterns of episodic memory and spatial navigation associated with normal aging and Alzheimer's disease. These patterns are discussed according to the multifactorial model of aging and the objective assessment of daily difficulties.The application of this research to the development of aids for the autonomy of the elderly is proposed as a work perspective.

A ce jour, nous savons peu de choses sur la manière dont la mémoire épisodique quotidienne, visuellement riche et complexe en termes d’éléments contextuels, est affectée par le vieillissement normal contrairement aux connaissances acquises dans le domaine du vieillissement sur la mémoire épisodique verbale ou visuelle au moyens des tests traditionnels ou des procédures de laboratoire comme le paradigme de rappel libres multi-essais (e.g., utilisé par le California Verbal Learning Test). La présente thèse s’est par conséquent attachée à implémenter ce paradigme traditionnel de rappels libres multi-essais d’évaluation de la mémoire épisodique au sein d’un dispositif RV simulant une visite dans un appartement, le HOMES test (Human Objet Memory of Everyday Scenes test). Cette procédure permet de dériver des indices d’apprentissage, de catégorisation, d’interférence proactive, de bénéfice de la reconnaissance comparée au rappel libre, et de fausses reconnaissances. A cela, nous nous sommes intéressés aux relations entre la mémoire quotidienne et l’action à travers l’effet denavigation active.A l’aide d’études comparatives, nous avons retrouvé le profil mnésique classiquement observé avec le test « papier-crayon », excepté pour l’interférence proactive qui n’est pas observée comme augmentée chez les participants âgés. En effet, des scores de rappel réduits,un bénéfice accru de la reconnaissance, une sensibilité augmentée aux fausses reconnaissances, et des capacités de regroupements sémantiques sont obtenus. Chez les jeunes adultes avec traumatisme crânien (étude 1), un profil identique est observé alors qu’un profil bien différent est obtenu auprès des patients avec maladie Alzheimer (étude 2) avec notamment un tableau associant des déficits plus marqués et des capacités de catégorisation altérées. Les études 3 et 4 adressant l’effet de navigation active chez le sujet jeune et âgé, ont mis en évidence un effet bénéfique de la navigation active sur la reconnaissance chez les deux groupes de sujets. Par contre, la navigation active diminuait les fausses reconnaissances des jeunes mais augmentait celles des âgés. Nous discutons les résultats de ces études sur la mémoire quotidienne à travers les hypothèses de déficit-item spécifique et du déclin fronto-exécutif du vieillissement normal. / To this day, very little is known about the way aging affects everyday episodic memory, which is a visually and contextually rich and complex memory. However, episodic memory is traditionally assessed using verbal tasks which are lacking such complexity. One of them, the California Verbal Learning Test (CVLT) uses the multi-trial free recall paradigm that we also implemented in the Human Object Memory of Everyday Scenes test using virtual reality to simulate a visit in an apartment (the HOMES test).This procedure allowed us to assess multiple memory processes such as learning, semantic clustering, proactive interference, recall versus recognition, and false recognitions. We also wanted to investigate the relationship between everyday memory and action through active navigation and its effects on each of these processes. We showed the typical profile of older adults usually obsereved using traditional paper-pencil tests on most of the memory indices except for proactive interference, which was not increased. In fact, older adults showed a reduced free recall performance despite a preserved learning ability across trials, a benefit from recognition but also a higher susceptibility to false recognitions. TBI patients (study 1) showed a profile similar to that of older adults, but patients with Alzheimer disease were impaired on all of the HOMES indices (study 2). Studies 3 and 4 examined the beneficial effect of active navigation in younger and older adults’ everyday memory and showed that that recognition was the measure that benefited the most in both age groups. In contrast, older adults while active navigation decreased false recognitions in younger adults, it actually increased false recognitions in older adults. Our results on everyday memory are discussed in terms of item-specific deficit and executive deficit hypotheses in normal aging.

Les tumeurs de la fosse postérieure (PFT) représentent les deux tiers des tumeurs cérébrales pédiatriques. Les PFT malignes les plus fréquentes sont le médulloblastome (40%), suivie de l'épendymome (10%). La chirurgie, la radiothérapie et/ou la chimiothérapie sont les approches thérapeutiques utilisées à l’heure actuelle. En raison de l'amélioration des traitements, la survie a augmenté de façon significative. Cependant, ces enfants souffrent de déficiences cognitives variées en partie attribuées à la radiothérapie et ce d’autant plus qu’ils sont jeunes. Atténuer les séquelles neurocognitives est devenu ces dernières années un des enjeux majeurs de l'oncologie pédiatrique. Dans cette optique, ce travail examine chez des enfants traités pour une PFT, les relations entre doses de radiothérapie reçues et performances neuropsychologiques en fonction de l’âge, au moyen d’une approche associant la neuroimagerie et la neuropsychologie. La contribution expérimentale s’articule autour de deux principaux axes. Le 1er axe utilise une approche exploratoire pour rendre compte des relations entre l’irradiation des régions cérébrales et le déclin cognitif chez les enfants traités pour une PFT. L’analyse des données met en relation des patterns spatiaux de répartition des doses dans le cerveau avec la variation des scores neuropsychologiques dans le temps (Mémoire de travail, vitesse de traitement, QI). Nos principaux résultats suggèrent une association entre la diminution des capacités en mémoire de travail et l’augmentation des doses (Dose uniforme équivalente, EUD) délivrées aux régions orbitofrontales ; alors qu’un ralentissement de la vitesse de traitement semble être lié à une dose élevée dans les lobes temporaux et la fosse postérieure. Le 2nd axe utilise une approche a priori pour déterminer l’impact de la maladie et des traitements sur le développement de la mémoire épisodique (ME) et des hippocampes, chez de jeunes enfants (2-13 ans). Cette partie se structure autour d’une part de l’analyse des performances des patients lors d’une tâche expérimentale mesurant la ME et d’autre part, d’une analyse longitudinale des volumes hippocampiques de ces enfants pendant le traitement. Nous avons a mis en évidence chez les enfants avec PFT une altération de la ME dépendant de l’âge : Chez les patients plus jeunes (<7 ans), l'altération était globale tandis que chez les plus âgés, elle ne concernait que la reconnaissance à long terme des détails temporels (c'est-à-dire «quand»). L’analyse des données volumiques hippocampiques n’a pas pu être achevée dans le temps de cette thèse, compte tenu de plusieurs difficultés méthodologiques liées notamment au recalage longitudinal des cerveaux en croissance. Ce travail apporte des connaissances nouvelles sur le rôle de certains facteurs dans l’émergence de difficultés cognitives spécifiques. La prévention des séquelles à long terme de ces enfants reste un défi pour les années à venir. / Pediatric posterior fossa tumors (PFT) account for two-thirds of all pediatric brain tumors. The most common malignant PFT is medulloblastoma (40%), followed by ependymoma (10%). Surgery, radiotherapy and/or chemotherapy are the current therapeutic approaches. As a result of the progress of treatment, event-free survival has significantly improved. Unfortunately, these children suffer from many cognitive impairments partly attributed to radiotherapy, especially in young children. Alleviating neurocognitive impairments has become one of the major challenges of pediatric oncology. Using an approach combining neuroimaging and neuropsychology, this work examines the relationship between treatments and neuropsychological performances as a function of age in children treated for PFT. The experimental contribution is based on two main axes. The first axis uses an exploratory approach to investigate the relationship between the decline of intellectual functioning and radiation dose distribution. For this purpose, we analyze, with a whole brain analysis, the relation between regional biological dose and changes over time of different cognitive scores (IQ, processing speed and working memory). Our results suggest a positive association between working memory decline and high dose (Equivalent Uniform Dose, EUD) delivered to the orbitofrontal regions, whereas decline of processing speed seems more related to EUD in the temporal lobes and posterior fossa. The 2nd axis uses a hypothesis-driven approach to determine the susceptibility of episodic memory (EM) impairment and hippocampal alteration in young child PFT patients (2-13yo). This part is structured around two aims: First, the assessment of PFT EM performances, thanks to an EM task, in comparison to Controls; second, the exploration of longitudinal patterns of hippocampal volume as a potential neural substrate underlying EM performance. The main results support the evidence of EM impairment in the PFT condition, which varied according to age: in the younger patients (<7yo) impairment was global while in the older it involved only the long term recognition of temporal details (i.e. ‘When’). However, at this stage of the work, several methodological difficulties mainly related to the registration parameters of the segmentation algorithm prevent us from achieving hippocampal volume analysis. This work brings new knowledge about the role of some risk factors on specific cognitive difficulties. Preventing long-term impairments of these children remains a challenge for years to come.

Introdução: A memória prospectiva (MP) refere-se a um conjunto de habilidades cognitivas que permitem lembrar-se de uma intenção a desempenhar no futuro, no momento adequado. Essa função é pouco avaliada em baterias neuropsicológicas que avaliam pessoas com epilepsia. Objetivo: Estudamos o impacto da cirurgia para epilepsia sobre a MP, componente prospectivo, em pessoas submetidas a lobectomia temporal unilateral para controle de epilepsia refratária ao tratamento clínico. Métodos: Comparamos o desempenho de MP em pessoas com epilepsia associada à esclerose mesial temporal à esquerda (EMTE) ou direita (EMTD) com dois grupos controles. Um grupo foi composto por indivíduos sem epilepsia (controles normais), e o outro por pessoas com epilepsia secundária à EMT, submetidos a avaliação e reavaliação neuropsicológica, sem intervenção cirúrgica (grupo clínico para controle teste/reteste). Resultados: Avaliamos 42 indivíduos sem epilepsia, 20 do grupo clínico (controle teste/reteste) e 39 do grupo cirúrgico (pré e pósoperatório). Comparamos o desempenho entre grupos e também a variação de desempenho individual, pelo índice de mudança confiável. Os grupos não diferiram em idade, escolaridade e quociente de inteligência. Na avaliação inicial, observou-se rebaixamento no desempenho em MP nos grupos clínico e cirúrgico (p < 0,01) (efeito lesão), sem diferença entre os grupos EMTE ou EMTD (efeito lateralidade). Para o grupo cirúrgico, observamos acentuada (p < 0,01) redução de crises e leve, porém significativa, redução de carga de drogas antiepilépticas pós-operatória. Observamos estabilidade em reteste de MP, declínio de memória verbal para o grupo EMTE e estabilidade de memória verbal e visual para o grupo EMTD. Conclusão: Embora exista um sistema de evocação compartilhado entre a MP e a memória episódica, a ressecção de estruturas temporais mesiais acometidas patologicamente não provoca declínio adicional em MP, mesmo quando se observou declínio de memória verbal no grupo EMTE. O comportamento dissociado de declínio de memória verbal para o grupo EMTE e preservação de MP após cirurgia de epilepsia sugere diferentes papeis das estruturas temporais mesiais nestes sistemas de memória. O papel do acometimento de estruturas extratemporais e de estruturas temporais não mesiais na MP em pacientes com EMT deverá ser melhor elucidado em estudos futuros / Introduction: Prospective memory (PM) refers to a set of cognitive abilities that allow recall of a previous intention to perform in the future, in the appropriate setting. This function is not usually evaluated in neuropsychological batteries used to evaluate people with epilepsy. Objective: We evaluated the impact of epilepsy surgery on the prospective component of PM, in people undergoing unilateral temporal lobectomy to treat medically refractory epilepsy. Methods: We compared performance in PM in people with left or right mesial temporal sclerosis (MTS) in the pre and postoperative periods with that of two control groups. One group was composed of people without epilepsy (normal controls), and another group was composed of people with epilepsy associated with mesial temporal sclerosis that underwent neuropsychological testing and retesting without undergoing surgery (clinical test/retest control group). Results: We studied 42 people without epilepsy, 20 clinical controls (test/retest group), and 39 patients that underwent epilepsy surgery (pre and postoperative testing). We compared groups performances and changes in individual performances with the reliable change index. Groups did not differ in age, education, and intelligence quotient. We found decreased preoperative PM performance for the clinical and surgical groups (p < 0.01) (lesion effect), without a difference between right and left groups (laterality effect). Postoperatively, there was a significant (p < 0.01) decrease in number of seizures, a small, but significant reduction in antiepileptic drug load, stable prospective memory, verbal and visual memory for right mesial temporal sclerosis, and decreased verbal memory in the left mesial temporal sclerosis group. Conclusion: In spite of a shared evocation system for episodic and prospective memory, resection of pathologically involved mesial temporal structures does not impact on prospective memory performance, even in the setting verbal memory decline in the left MTS group.The finding of dissociated verbal memory decline and PM stability after epilepsy surgery suggests a different role of mesial temporal lobe structures in these memory systems. The role of extratemporal and nonmesial temporal lobe structures in prospective memory in MTS patients should be evaluated in future studies