Animals learn from past experience to guide future behavior and improve survival. This ability relies in part on specific episodic memories of past events encoded by neuronal activity and stored by updated connectivity between neurons. The unique architecture and activity of the hippocampus and related cortical regions are crucial for supporting these episodic memories. Hippocampal models propose the need for a pattern separation function to disambiguate similar memories and a pattern completion function to recall the full breadth of an experience from a partial cue. Past work suggests that neuronal activity in the dentate gyrus (DG) of hippocampus contributes to memory-guided navigation and plays a role in pattern separation. We tested the role of specific DG neuronal ensembles (i.e. engrams) in supporting the pattern separation function and altering downstream neural activity and, ultimately, behavior. To that end, we used an activity-dependent labeling paradigm to identify and manipulate engram ensembles during navigational and contextual fear conditioning (CFC) tasks. The results of our first experiment revealed that the DG partially disambiguates specific maze trajectories while still exhibiting greater overlap than chance levels. These findings suggest that the DG contributes to memory-guided navigation by both pattern separation and completion. Our second experiment manipulated nonspecific memory-related DG populations to assess the functional role of these cells in task generalization across contexts and ongoing spatial working memory. Optogenetic activation of these ensembles disrupted performance accuracy and exhibited a time-dependent impairment effect suggesting a role of the DG in task generalization between contexts. The final experiments investigated the physiological ramifications of artificial memory ensemble reactivation during ongoing navigation behavior. We recorded local field potential (LFP) and single unit responses in mouse DG and CA1 during artificial reactivation of a DG-mediated CFC memory engram. Stimulation of the DG entrained LFP and individual cell spiking in a subpopulation of CA1 pyramidal cells. Their spatial information was disrupted by stimulation despite stable navigational representation before and after the manipulation. Further, the presence of stimulation could be reliably decoded by the firing rate of the network, suggesting that engram reactivation forced the CA1 to adopt a repeatable state, perhaps to support behavioral expression of memories. In summary, my dissertation work presents empirical and theoretical evidence for the role of the dentate gyrus as a single node of an extended separation/completion circuit distributed anatomically and temporally as a neural mechanism supporting episodic memory.

<p>Research on backward response compatibility effects (Task 2-to-Task 1 response priming) in the Psychological Refractory Period (PRP) paradigm has suggested that compatibility effects arise from episodic representations of Stimulus-Response (S-R) pairings (Hommel & Eglau, 2002). However, more recent work suggests that these effects are mediated by S-R rules held online in working memory during dual task performance (Ellenbogen & Meiran, 2008). We sought to dissociate these accounts. In Experiment 1, we observed the development of backward response compatibility effects over time in a common PRP task, following varying degrees of prior single task practice of the PRP component tasks. In Experiment 2, we trained participants on a PRP dual task, and then switched Task 2 to one of three different tasks with variable response mapping overlap with the original Task 2, before finally reverting back to the original PRP tasks. Backward response compatibility effects appeared initially, were abolished during the subsequent interference phase, and then reappeared with the original PRP task. Despite equivalent overall performance across conditions suggesting successful task rule instantiation in working memory to guide task performance, backward response compatibility effects were selectively absent in conditions where current S-R rules were mapped in conflict with prior S-R experiences within the experiment. Both experiments provide evidence in favour of an episodic account of backward response compatibility effects, in which prior learning influences subsequent performance in contextually relevant situations. Implications for the understanding of backward response compatibility mechanisms and parallel processing in the PRP paradigm are discussed.</p> / Master of Science (MSc)

Yes / Background: The face-name association technique (FNAT) is commonly used to investigate name recall in nonpathologic aging. This technique is appropriate for studying anomia, but the pure-list technique, in which participants see only names and do not need to form face-name associations, might be more appropriate for studying age-related name recall. Methods: Experiment 1 recruited 60 adults (30 younger and 30 older adults) to participate in the FNAT recognition task of 30 common and 30 uncommon names. In experiment 2, the same number and demographic of participants attempted to recall 30 common and 30 uncommon names. Both experiments utilized measurements of overall recall across 5 trials and a delayed recognition or recall trial. Measures of encoding (gained access) and consolidation (lost access) were also taken for the 5 initial trials in both experiments. Older participants received 50% extra study and recognition/recall time. Results: The FNAT experiment revealed an age-related episodic memory deficit for names. However, in cued recall, encoding, consolidation, retention/retrieval, and false alarm tests, older adults were significantly better than younger adults at recalling uncommon names, as opposed to common names. This lends support to the inhibition theory of name recall. Conversely, our second experiment revealed no age effect on any factors of name memory functioning, supporting node structure theory. Conclusions: The results of our experiments support previous findings that suggest an age-related deficit in name recall, but only in cases of anomia. Therefore, the FNAT methodology may be inappropriate for studying age-related name recall. It is possible that names are stored in the memory differently from nouns. We challenge the belief that older adults are significantly less able to recall names compared with other word types, which has implications for both memory self-efficacy questionnaires and research into eye-witness testimonies.

Cognitive processes in the human brain are mediated by complex interactions among distributed brain regions. The interaction between the hippocampus and neocortical regions is crucial for physiologic and pathologic long-term episodic memory processing in the brain. However, the network mechanisms of this hippocampal-cortical communication remain unclear. To address this issue, we first designed organic materials and conformable electronics to create integrated neural interface devices that increase the spatiotemporal resolution of electrophysiologic monitoring. These devices enabled acquisition of local field potentials and action potentials of individual cortical neurons from the surface of the human brain, enhancing the ability to investigate neural network mechanisms without breaching the tissue interface. Next, we employed these devices in tandem with hippocampal probes to analyze hippocampal-cortical interactions in the context of memory tasks in freely moving rodents. We determined that in the physiologic state, the spatial properties of cortical spindle oscillations predict the likelihood of coupling with hippocampal ripples and are modulated by memory demand. In the pathologic state, we showed that interictal epileptiform discharges (IEDs), ubiquitous markers of epileptic networks, disrupt hippocampal-cortical coupling required for memory consolidation. These IEDs induce spindle oscillations in the synaptically connected cortex, producing prolonged, hypersynchronous neuronal spiking and expanding the brain territory capable of generating IEDs. Spatiotemporally targeted closed-loop electrical stimulation triggered on hippocampal IED occurrence eliminated the abnormal cortical activity patterns, preventing spread of the epileptic network and ameliorating long-term spatial memory deficits in rodents. Our findings provide new insights into mechanisms of physiologic and pathologic memory processing and offer novel approaches to therapies aimed at addressing distributed network dysfunction in neuropsychiatric disorders.

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

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.

Quick work out sessions has been shown to improve students’ academic performance. Furthermore, certain cognitive functions have also been shown to improve academic performance. The aim of this study was therefore to investigate if quick work out sessions can improve certain cognitive functions and whether these functions could act as mediator variables between exercise and academic performance. Thirty participants were randomly assigned to a control group that was shown a music video (n=15) and an experiment group that was asked to use a step up exercise device (n=15). Cognitive shifting, episodic memory and perceptual speed were tested in both groups, before and after the intervention. The result didn’t show a significant effect on any cognitive function. This might be explained by the low amount of participants, considering that similar studies often have small effects.Key words: acute exercise, cognitive shifting, episodic memory, perceptual speed. / Korta träningspass har visat sig förbättra elevers skolprestation. Vidare har också vissa kognitiva förmågor visat sig förbättra skolprestation. Denna studies syfte var därför att se om korta träningspass kan förbättra vissa kognitiva förmågor och huruvida dessa förmågor då skulle fungera som mediatorvariablermellan träning och skolprestation. Trettio deltagare delades slumpmässigt in i en kontrollgrupp som fick se en musikvideo (n=15) och en experimentgrupp som fick gå upp och ner för en step up-bräda (n=15). Kognitiv skiftning, episodiskt minne och mentalt tempo testades i båda grupper, före och efter interventionen. Resultatet visade inte på någon signifikant effekt på någon kognitiv förmåga. Detta kan bero på det låga antalet deltagare, då effekter av liknande studier ofta är små.