Fine motor skills are learned through repetitive practice and once learned, last for a long time. Skilled reaching is linked to structural and functional changes in multiple brain regions including, in particular, the primary motor cortex. Previous studies demonstrated that fine motor skill learning is associated with cortical synaptogenesis and motor map reorganization. At present, studies have implicated an indispensable role of epigenetic alterations in both hippocampal- and striatal-dependent memory formations, while examinations into the epigenetic changes in the primary motor cortex are lacking. The current study was aimed to identify epigenetic changes in motor cortex as a result of extensive motor skill learning using the single pellet skilled reaching task. Male Wistar rats were trained in the single pellet skilled reaching task (n = 6) for 10 consecutive days or were, under similar conditions, given access to pellets that did not require skilled reaches (n = 6). Skilled motor trained rats exhibited a rapid increase in successful reaches during the first four days of motor training before reaching a plateau, indicative of the acquisition and consolidation of the learned task, respectively. Expression profiles of chromatin modifying enzymes were screened using epigenetic-targeted PCR arrays. Results suggest that gene expression levels of multiple chromatin regulatory enzymes were down-regulated in the motor cortex of trained animals compared to controls following 10 days of motor training in the skilled reaching task. Among the chromatin modifying enzymes, the transcription level of Smyd1 (SET and MYND domain containing 1; NM_001106595) was lower (-2.17 fold-change) in motor cortex after 10 days of training compared to controls. Our results point to an epigenetic regulation of chromatin modification markers in the primary motor cortex that possibly underlie the mechanisms of synaptic plasticity, synaptogenesis and the formation of procedural memory.

Unlike other domains of cognition, the acquisition of procedural skills (e.g., the "how to" of memory) is spared by age. However, the consolidation (i.e., the transformation from labile memory to long-term storage) of this type of memory is compromised by age. Optimal memory consolidation for procedural skills is dependent on sleep. Sleep is also negatively impacted by normal, healthy aging. Recent research has identified the neural markers of the lost benefit of sleep for reduced memory consolidation with age. While this is relatively well-established for procedural memory, and for cognitively simple motor skills, the impact of age-related changes in sleep on cognitively complex procedural memory consolidation (i.e., novel cognitive strategies required for "problem-solving skills") remains to be investigated. Furthermore, reduced capacity to solve problems with age has serious mental health-related consequences, including increased depression and suicide attempts, as well as disability in depressed, cognitively impaired older adults. Moreover, problem-solving therapy has been found to improve quality of life in older adults. As such, the aims of these series of studies were to investigate: 1) the behavioural consequences of age on sleep-dependent memory consolidation, 2) identify the electrophysiological markers during sleep of the lost benefit of sleep, 3) identify the age-related changes in brain structure and how this relates to and behavioural outcomes and sleep, and, 4) identify the impact of age on sleep-dependent consolidation of the memory trace for problem-solving skills. Using an innovative combination of EEG, MRI, and behavioural testing in healthy young and older adults, these series of studies revealed novel insights into the breakdown of the normal processes that occur during sleep that support memory. The main objective of this thesis is to identify the neural markers of the very earliest signs under optimal conditions of age-related cognitive decline for problem-solving skills. Investigating the neurophysiological and behavioral consequences of age-related changes in sleep, and their impact on problem-solving skills, will help reveal therapeutic targets for future research that will improve quality of life for seniors. Furthermore, this research will ultimately lead to the development of early interventions targeting sleep that could delay or lessen the severity of the onset of clinically significant cognitive impairment; as those who sleep better, may also age better cognitively.

No description available.

The procedural deficit hypothesis (PDH) posits that a range of language, cognitive and motor impairments associated with specific language impairment (SLI) and developmental dyslexia (DD) may be explained by an underlying domain-general dysfunction of the procedural memory system. In contrast, declarative memory is hypothesized to remain intact and to play a compensatory role in the two disorders. The studies in the present thesis were designed to test this hypothesis. Study I examined non-language procedural memory, specifically implicit sequence learning, in children with SLI. It was shown that children with poor performance on tests of grammar were impaired at consolidation of procedural memory compared to children with normal grammar. These findings support the PDH and are line with previous studies suggesting a link between grammar processing and procedural memory. In Study II, the same implicit sequence learning paradigm was used to test procedural memory in children with DD. The DD group showed a learning profile that was similar to that of children with SLI in Study I, with a significant impairment emerging late in learning, after extended practice and including an overnight interval. Further analyses suggested that the DD impairment may not be related to overnight consolidation but to the effects of further practice beyond the initial practice session. In contrast to the predictions of the PDH, the sequence learning deficit was unrelated to phonological processing skills as assessed with a nonword repetition task. Study III examined declarative memory in DD. The performance of the DD group was found to be not only intact, but even enhanced, compared to that of the control children. The results encourage further studies on the potential of declarative memory to compensate for the reading problems in DD. In sum, the results lend partial support for the PDH and suggest further refinements to the theory. Collectively, the studies emphasize the importance of going beyond a narrow focus on language learning and memory functions in the characterization of the two disorders. Such a broader cognitive, motor and language approach may inform the development of future clinical and pedagogical assessment and intervention practices for SLI and DD.

Le vieillissement, normal ou pathologique, s’accompagne de déficits marqués de la mémoire épisodique et de la mémoire de travail. Dès lors, est-il possible d’optimiser l’apprentissage moteur en s’appuyant sur d’autres registres de mémoire éventuellement moins affectés, voire épargnés, par les effets du temps ? Dans les trois expériences que nous avons menées, la prédominance d’un registre de mémoire sur un autre a été manipulée en contrastant les effets, lors de la réalisation de 160 essais d’une tâche sensorimotrice (le putting au golf), de deux méthodes distinctes d’apprentissage : la méthode en condition d’erreurs fréquentes supposée solliciter les processus mnésiques déclaratifs (mémoire épisodique et mémoire de travail) vs la méthode en condition d’erreurs peu fréquentes supposée solliciter les processus mnésiques procéduraux. Dans l’Étude 1, nous avons testé, chez des adultes jeunes et âgés, l’efficacité de ces méthodes et la nature des processus en jeu lors de la réalisation simultanée d’une tâche secondaire coûteuse en attention. Dans l’Étude 2, nous avons comparé les performances motrices entre des adultes jeunes, plus âgés, et des patients Alzheimer. Dans l’Étude 3, nous avons évalué les effets de la verbalisation des actions motrices produites durant l’apprentissage sur les processus mnésiques sous-tendant la performance motrice d’adultes jeunes et plus âgés. Les résultats de l’Étude 1 montrent que l’apprentissage est affecté par le vieillissement lorsque prédominent les processus déclaratifs mais qu’il est préservé des effets du temps lorsque prédominent les processus procéduraux. Les résultats de l’Étude 2 démontrent que l’apprentissage est préservé des effets de la maladie d’Alzheimer lorsque prédominent les processus procéduraux. Les résultats de l’Étude 3 révèlent que la verbalisation affecte les processus déclaratifs mais n’a pas d’effet sur les processus procéduraux chez les adultes jeunes et qu’elle n’a aucun effet sur ces deux types de processus chez les adultes plus âgés. Ces résultats attestent qu’il est possible de « contourner » la mémoire déclarative et les déficits survenant avec l’âge ou avec la maladie en s’appuyant sur une mémoire procédurale intacte, ce qui a pour effet d’optimiser l’apprentissage moteur. / Normal or pathological aging is characterized by specific deficits in episodic and working memories. Therefore, is it possible to optimize motor learning with advancing age, by utilizing other memory processes hypothesized to be less affected or even spared from aging? We conducted three experiments in which the predominance of one memory system over another was manipulated by contrasting the effects, across 160 trials of a sensorimotor task (golf putting), of two different learning methods: the infrequent-error method hypothesized to primarily rely upon declarative memory vs. the frequent–error method hypothesized to primarily rely upon procedural memory. In Experiment 1, we tested in young and older adults the efficiency of these methods and the nature of processes involved when a secondary, attention-demanding task was performed concurrently. In Experiment 2, we compared the motor performance between young and older adults and Alzheimer patients. In Experiment 3, we assessed the effects of verbalizing previous motor actions produced during learning on processes underlying young and older adults’ motor performance. The results of Experiment 1 showed that learning is affected by aging when declarative processes are predominant but is protected from advancing age when procedural processes are predominant. The results of Experiment 2 demonstrated that learning is preserved from Alzheimer’s disease when procedural processes are predominant. The results of Experiment 3 revealed that verbalization affects declarative processes but has no effect on procedural processes in young adults, and that it has no effect on these two types of processes in older adults. Altogether, these results show that “bypassing” declarative memory and its deficits occurring with advancing age or disease is doable by utilizing intact procedural memory, thus leading to an optimized motor learning.

Ce travail de thèse avait pour objectif principal de contribuer à une meilleure compréhension de la mémoire procédurale dans le vieillissement normal et pathologique. Plus spécifiquement, nous avons tenté de déterminer de manière plus précise limpact du mode dentraînement afin didentifier les conditions qui optimisent lacquisition de nouvelles habiletés dans le vieillissement normal et pathologique. Avant dexaminer plus précisément les implications de nos résultats sur les plans théorique et clinique, il convient tout dabord den faire un bref récapitulatif. LEtude 1 comportait un double objectif : (1) développer une épreuve évaluant lacquisition de nouvelles habiletés perceptivo-motrices qui serait facilement applicable dans un contexte clinique ; (2) étudier limpact du mode dentraînement sur lacquisition de ces nouvelles habiletés chez des sujets adultes. Dans cette perspective, nous avons créé une version informatisée du paradigme de dessin en miroir. Dans cette tâche, les sujets devaient parcourir des figures géométriques, le plus rapidement possible, à laide dune souris dordinateur inversée. Afin de poursuivre nos objectifs, trois expérimentations ont été menées. Dans lexpérience 1, deux types dentraînement étaient comparés : un entraînement constant et un entraînement variable. Nous pensions que ce dernier engendrerait de plus faibles performances durant la phase dacquisition, mais de meilleures performances lors de la phase test. Cependant, aucune différence de performance nest apparue entre les deux conditions. Nous avons, dès lors, supposé que cette absence de différence puisse être liée à la nature de linstruction donnée aux participants exigeant une grande rapidité. Ainsi, les sujets de la condition constante, parce quils réalisaient la tâche à la limite de leurs possibilités, se trouvaient de facto dans une condition comparable (en termes dinvestissement) à la condition variable. Dans lexpérience 2, une limitation de vitesse a été imposée sur les mêmes tâches afin de renforcer le contraste entre les conditions constante et variable. Cependant, aucune différence nest apparue entre les groupes. A nouveau, nous avons postulé que la méthodologie employée nétait pas en mesure de mettre en évidence une différence entre les modes dentraînement. En effet, durant lexpérimentation, il est apparu que les sujets des deux groupes commettaient de nombreuses erreurs engeandrant à leur tour un ralentissement du déplacement de la cible, obligeant donc les sujets à freiner et constamment contrôler leur mouvement. Par conséquent, il est possible que ce contrôle ait pu à nouveau rendre la condition constante comparable à la condition variable en termes dinvestissement cognitif. Nous avons dés lors proposé une nouvelle consigne durant la phase dacquisition de lexpérience 3 : réaliser le parcours en commettant le moins derreurs possible et sans contrainte de temps. Cette nouvelle adaptation na pas, une fois encore, permis de mettre en évidence de différence dapprentissage entre les diverses conditions dentraînement (constante, bloc et variable). Ces résultats suggèrent que la tâche de dessin en miroir informatisée était trop complexe pour mettre en avant un effet du mode dentraînement. LEtude 2 comportait également un double objectif : (1) créer une épreuve de lecture en miroir permettant dévaluer de manière plus précise lacquisition de nouvelles habiletés perceptivo-verbales ; (2) explorer plus spécifiquement ces capacités dans le vieillissement normal et dans la maladie dAlzheimer. En effet, après avoir remis en question la pertinence du paradigme de lecture en miroir de Cohen et Squire (1980), Masson (1986) a créé un nouveau paradigme mais navait, de façon étonnante, pas observé dapprentissage procédural chez des sujets jeunes. Dans ce contexte, nous avons apporté plusieurs modifications (lettres majuscules, non-mots, sens de lecture) à ce paradigme afin de le rendre plus efficace dans lévaluation de lapprentissage procédural. Ainsi, notre première expérience montre chez des sujets jeunes un apprentissage avec une amélioration des performances entre la phase dacquisition et la phase test tant pour des non-mots composés de lettres déjà traitées que pour des non-mots composés de nouvelles lettres encore jamais vues. Ces résultats suggéraient donc que la nouvelle version de cette tâche permettait dévaluer lapprentissage procédural et non plus un effet damorçage de répétition sur les lettres. Lors dune seconde expérience, nous avons donc mis à profit cette tâche pour évaluer lapprentissage de nouvelles habiletés perceptivo-verbales de manière plus fine et adaptée dans la maladie dAlzheimer. Les résultats ont mis en évidence un effet damorçage de répétition chez les patients et les sujets âgés de contrôle mais un apprentissage procédural uniquement chez les sujets âgés de contrôle. Cette incapacité pourrait remettre en question lidée générale selon laquelle lapprentissage procédural est généralement préservé dans cette pathologie. Toutefois, la difficulté des patients à acquérir cette habileté pourrait être liée à une trop grande variabilité de la tâche utilisée. Dès lors, administrer cette même épreuve selon un mode plus constant pourrait permettre aux patients, par une diminution du recours aux processus contrôlés, dacquérir cette habileté de lecture en miroir. Toujours dans le but dexplorer les capacités de mémoire procédurale dans le vieillissement pathologique, lEtude 3 a investigué cet aspect dans la démence à corps de Lewy (DCL). Bien quun intérêt grandissant est né pour cette pathologie depuis quelques années, aucune étude na jusquici tenté dy investiguer le statut de la mémoire procédurale. Les résultats ainsi obtenus montraient que les patients DCL, tout comme les sujets âgés, amélioraient leurs performances entre la phase dacquisition et la phase test tant pour les lettres déjà rencontrées que pour les nouvelles lettres. Dans lEtude 4, nous avons voulu déterminer si un mode dentraînement caractérisé par une plus faible variabilité, permettrait aux patients Alzheimer dacquérir lhabileté de lecture en miroir. Concrètement, cette étude comportait également un double objectif : (1) investiguer limpact du mode dentraînement (bloc versus variable) dans un domaine perceptivo-verbal chez des patients Alzheimer ; (2) tester lhypothèse selon laquelle un entraînement variable est caractérisé par un recours plus important au fonctionnement exécutif quun entraînement en bloc. Vingt-quatre patients Alzheimer ont été testés et deux conditions dentraînement ont été comparées. La condition en bloc consistait à présenter des non-mots construits avec une première série de lettres (série A) et ensuite présenter des non-mots avec une autre série de lettres (série B). En revanche, dans la pratique variable, lensemble des non-mots étaient construits avec des lettres appartenant aux séries A et B simultanément. Il est apparu que les patients issus de la condition en bloc lisaient les non-mots composés de nouvelles lettres significativement plus vite que le groupe variable, qui lui, na pas amélioré sa performance. De plus, nos résultats ont confirmé limplication du fonctionnement exécutif dans la pratique variable et non dans la pratique en bloc. Ces résultats montrent que des patients déficitaires sur le plan exécutif auront plus de difficultés à apprendre de nouvelles habiletés perceptivo-verbales au travers dun entraînement variable.

Made available in DSpace on 2015-05-14T12:43:03Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1310227 bytes, checksum: 04da33952d4cd23496fa53ef618ff840 (MD5) Previous issue date: 2014-03-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This dissertation aims to explain how is the processing of coreference in people who stutter (PWS), reflecting on the possibility of an association between stuttering and the presence of difficulties in procedural memory, from the relationship between Alm's Dual Premotor Model (2005) and Ullman´s Declarative/Procedural Model (2001). It is proposed, then, a hypothesis about the connection between the presence of dysfunctions in procedural memory and the linguistic processing of PQG, which was investigated through the ASRT test (Alternating Serial Reaction Time) of procedural memory and two experiments of self-paced reading to the investigation of the phenomenon of inter and intrasentential coreference. In the ASRT test (experiment 1) performed to measure the degree of implicit learning of the participants, the findings suggested a tendency of the groups (PQC and FF) to behave distinctively. PQG showed a pattern of ascending curve, with a positive Spearman's coefficient for the variable cycle, expressing an increase in time of reaction as it increased the number of cycles (stimuli). Which we interpreted as a possible difficulty in the PQG in implicit learning of motor sequences. And the FF showed a descending curve, confirmed by a negative Spearman's coefficient for the variable cycle. Demonstrating that the procedural learning for this group occurred quickly, i.e., the reaction time of the FF reduced as there was an increase in the number of cycles. With these indications that PQG present difficulties in procedural memory, which could interfere in the processing of grammatical aspects according to our hypothesis, we set out to the investigation of the linguistic processing. In experiment 2, the intersentential coreference, performed with the aim at investigating the processing of lexical pronoun (PR) and the repeated name (NR) in the object position between FF and PQC, the results showed that there is no difference in this type of processing between FF and PQC, since both groups showed similar patterns in the average reading time of the critical segment. However, there were a significant effect for the variable tipo de retomada, showing that PR are processed faster than the NR, as previously found by Leitão (2005). Thus, in order to investigate how was grammar functioning in PQG and to attest the hypothesis defended in this dissertation, we set out to the analysis of the phenomenon of coreference in the intrassentential level, in order to isolate the grammatical aspect and eliminate possible interference from the pragmatic and contextual factors. The results pointed to the absence of main effect for the variable group, however, we found a marginally significant interaction effect between the variables group and type of sentence. This interaction can be explained by the fact that the groups react differently to the conditions, departing from the observation that there is an inverse behavior between them, i.e., to the extent that FF are faster in the grammatical condition and slower in agramatical condition, PQG show the opposite pattern. Which corroborates our hypothesis that PQG would have difficulties in perception of breach of grammatical principle. This possibility, confirmed by the statistical evidence foreseen for our findings with the increase of sample, that it directs our search for rejecting the null hypothesis. / Esta dissertação tem por objetivo explanar como se dá o processamento da correferência em pessoas que gaguejam (PQG), refletindo sobre a possibilidade de associação entre a gagueira e a presença de dificuldades na memória procedimental, a partir da relação entre o Modelo Pré-Motor Duplo de Alm (2005) e o Modelo Declarativo/Procedimental de Ullman (2001). Lança-se, então, uma hipótese acerca da conexão entre a presença de disfunções na memória procedimental e o processamento linguístico das PQG, investigada por meio do teste ASRT (Alternating Serial Reaction Time) de memória procedimental e dois experimentos de leitura automonitorada para a investigação do fenômeno da correferência inter e intrassentencial. No teste ASRT (experimento 1) realizado para medir o grau de aprendizagem implícita dos participantes, os resultados encontrados apontaram para uma tendência dos grupos (PQG e FF) a comportarem-se de maneira distinta. As PQG evidenciaram um padrão de curva ascendente, com coeficiente de Spearman positivo para a variável ciclo, expressando um aumento do tempo de reação à medida que se aumentava o número de ciclos (estímulos). O que interpretamos como uma possível dificuldade das PQG na aprendizagem implícita das sequências motoras. E os FF evidenciaram uma curva descendente, confirmada pelo coeficiente de Spearman negativo para a variável ciclo. Demonstrando que a aprendizagem procedimental para este grupo ocorreu de maneira mais rápida, ou seja, o tempo de reação dos FF reduzia à medida que se aumentava o número de ciclos. De posse desses indícios de que as PQG apresentam dificuldades na memória procedimental, o que poderia interferir no processamento dos aspectos gramaticais de acordo com a nossa hipótese, partimos para a investigação do processamento linguístico. No experimento 2, de correferência intersentencial, realizado com o intuito de investigar o processamento do pronome lexical (PR) e do nome repetido (NR) em posição de objeto entre FF e PQG, os resultados obtidos evidenciaram que não há diferença nesse tipo de processamento entre FF e PQG, uma vez que ambos os grupos apresentaram padrões semelhantes no tempo médio de leitura do segmento crítico. No entanto, houve efeito significativo para a variável tipo de retomada, constatando que os PR são mais rapidamente processados do que o NR, conforme já encontrado em Leitão (2005). Dessa forma, a fim de investigar como se dava o funcionamento da gramática nas PQG e atestar de modo mais categórico a hipótese defendida nesta dissertação, partimos para a análise do fenômeno da correferência em nível intrassentencial, objetivando isolar o aspecto gramatical e eliminar as possíveis interferências dos fatores pragmáticos e contextuais. Os resultados obtidos apontaram a ausência de efeito principal para a variável grupo, no entanto, constatou-se um efeito de interação marginalmente significativo entre as variáveis grupo e tipo de sentença. Essa interação pode ser explicada pelo fato de os grupos reagirem diferentemente às condições, partindo da observação que há um comportamento invertido entre eles, ou seja, na medida em que os FF s são mais rápidos na condição gramatical e mais lentos na condição agramatical, as PQG apresentam o padrão oposto. O que corrobora com a nossa hipótese de que as PQG teriam dificuldades na percepção da violação do princípio gramatical. Possibilidade essa, confirmada por meio das evidências estatísticas previstas para os nossos resultados com o aumento da amostra, que direciona a nossa pesquisa para a rejeição da hipótese nula.

A leading theory for why we sleep focuses on memory consolidation - the process of stabilizing and strengthening newly acquired memories into long-term storage. Consolidation of memory for cognitive strategies and problem-solving skills is enhanced as compared to a period of daytime wakefulness. Importantly, sleep preferentially enhances memory for the cognitive strategy per se, over-and-above the motor skills that are used to execute the strategy. Although it has been known for some time that sleep benefits this type of memory, it is not known how this process unfolds during sleep, or how sleep transforms this memory trace in the brain. Sleep is classified into rapid eye movement (REM) sleep and non-REM (NREM) sleep. The role of REM sleep for consolidation of memory for problem-solving skills remains controversial. In addition, little attention has been paid to the possible distinct roles of phasic REM sleep (i.e., when bursts of eye movements occur) and tonic REM sleep (i.e., the presence of isolated eye movements and the absence of eye movement bursts). REM sleep might favour procedural memory consolidation for cognitive strategies and problem-solving skills, and the specific role of REM sleep in this process might be discernible only by differentiating between phasic and tonic REM states. In addition, fMRI studies have revealed that sleep-related consolidation of the memory trace for simple motor procedural skills is associated with strengthened activity of, and functional connectivity between, key memory-related brain areas (i.e., hippocampal, striatal, and neocortex). However, fMRI techniques have not yet been employed to investigate sleep-related consolidation of procedural memory for cognitive strategies and problem-solving skills. Participants (n=60) performed a procedural memory task involving a cognitive strategy while undergoing functional magnetic resonance imaging (fMRI) before and after a condition of Sleep, Nap, or Wake. Those in the Sleep and Nap condition underwent polysomnography (PSG) to further study the learning-related changes in sleep macrostructure and microstructure. This thesis not only shows that a period of sleep or a nap afford a greater benefit to memory consolidation of a procedural strategy than a period of wake, but more specifically: In Study 1, during sleep, phasic REM sleep theta power was directly associated with overnight improvement on the task, whereas tonic REM sleep sensorimotor rhythm power was greater following a night of learning compared to a non-learning control night. In Study 2, we show that distinct hippocampal, striatal, and cortical areas associated with strategy learning are preferentially enhanced. Study 3 reveals that the functional communication among these brain areas is greater following sleep compared to a daytime nap or day of wakefulness. Sleep-related changes in brain activation and functional connectivity were both correlated with improved performance from before to after a period of sleep. Overall, findings from this thesis support the benefit of sleep at the behavioural and systems level for consolidating procedural memory involving cognitive strategies used to solve problems. The findings suggest that the multifaceted nature of REM sleep must be examined separately by its phasic and tonic states, to identify the active role of REM sleep for consolidating memory. Further, the consolidation of the memory trace is reflected through activation of, and communication between hippocampal, striatal, and neocortical brain areas. In summary, this thesis shows that sleep actively consolidates memory for cognitive strategies and problem-solving skills.

Dyslexi är en form av läs- och skrivsvårighet som inte kan förklaras av t.ex. bristfällig undervisning, låg begåvning eller synproblem. Orsaken till dyslexi anses vanligen vara nedsatt förmåga av fonologiskt processande. Flera studier har dock visat att dyslexi även är förknippat med språkliga, kognitiva och motoriska svårigheter som inte kan förklaras av nedsatt förmåga av fonologiskt processande. Det procedurella minnessystemet engageras vid inlärning, processande och konsolidering av kognitiva och motoriska färdigheter. Enligt the procedural deficit hypothesis (PDH) orsakas de svårigheter förekommande vid dyslexi av en nedsättning i detta minnessystem. Forskningen inom området är inte entydig då det har rapporterats om både intakt och nedsatt procedurellt minne hos personer med dyslexi. Föreliggande studie var den första att undersöka procedurellt minne hos svenska universitetsstuderande med dyslexi. Syftet var att testa PDH med hjälp av alternating serial reaction time task (ASRT), samt att undersöka relationen mellan procedurellt minne, närmare bestämt implicit sekvensinlärning, och läsförmåga samt aspekter av språklig/fonologisk förmåga. I studien deltog totalt 37 universitetsstuderande, 11 med dyslexi och 26 utan dyslexi. Resultatet indikerade att förmågan till inlärning och konsolidering i det procedurella minnet inte skilde sig åt mellan grupperna. Resultatet ger således inte stöd åt PDH. Vidare kunde inga signifikanta korrelationer påvisas, vilket tyder på att det inte föreligger något samband mellan procedurellt minne och respektive läsförmåga, fonologisk medvetenhet och snabb benämning (rapid automatized naming, RAN). / Developmental dyslexia is characterized by reading and writing difficulties that do not derive from poor education, low intelligence or visual impairment. The disorder is commonly explained as a result of an underlying phonological deficit. However, studies have shown that dyslexia is also associated with linguistic, cognitive, and motor impairments that can not be explained by a specific phonological deficit. The procedural memory underlies learning, processing and consolidation of motor and cognitive skills. The procedural deficit hypothesis (PDH) suggests that an impairment of procedural memory is the underlying cause of developmental dyslexia. Previous research has yielded inconsistent results as studies have reported intact as well as impaired procedural memory in dyslexics. This study was the first to examine procedural memory in Swedish university students. The aim was to test the PDH, by using an alternating serial reaction time task (ASRT), and to examine the correlation between procedural memory and reading ability as well as aspects of linguistic/phonological ability. In this study there was a total of 37 university students, 11 dyslexics and 26 nondyslexics. The result showed learning and consolidation of the procedural memory in both groups and there was no significant difference between the groups. Thus, the results do not support the PDH. No significant correlations were found, which indicates that there is no association between procedural memory and reading ability, phonological awareness or rapid automatized naming (RAN).

Les modifications post-traductionnelles des histones jouent un rôle majeur dans la régulation de l’expression de gènes impliqués dans la plasticité et la mémoire. Parmi ces modifications, l’acétylation des histones permet le maintien de la chromatine dans un état « permissif », accessible pour la transcription. Nos travaux visent à identifier le rôle joué par l’acétylation de deux histones, H3 et H4, dans la formation de différentes formes de mémoire mettant en jeu les systèmes hippocampique et striatal chez la souris. Nous avons également recherché si des perturbations d’acétylation des histones sont responsables des déficits mnésiques observés au cours du vieillissement. Nous avons utilisé deux types d’apprentissage en piscine de Morris permettant de dissocier la mémoire spatiale, impliquant principalement l’hippocampe et la mémoire procédurale/indicée, impliquant le striatum. Nos résultats mettent en lumière une régulation différentielle de l’acétylation des histones dans l’hippocampe et le striatum selon la nature de la tâche et l’âge des animaux. L’apprentissage spatial induit une augmentation de l’acétylation des histones sélectivement dans l’hippocampe (CA1 et gyrus denté) alors que la tâche indicée augmente l’acétylation des histones spécifiquement dans le striatum. Nous montrons également que des changements opposés de l’acétylation de H3 (augmentation) et de H4 (diminution) dans l’hippocampe pourraient contribuer aux déficits de mémoire spatiale observés chez les souris âgées. Lors d’un test de compétition en piscine de Morris, durant lequel les souris ont le choix entre les stratégies spatiale et indicée pour résoudre la tâche, l’injection intra-hippocampique de Trichostatine A (TSA), un inhibiteur des histones déacétylases, immédiatement après l’apprentissage, perturbe la fonction striatale et favorise l’utilisation préférentielle de la stratégie spatiale hippocampique. Cependant, cet effet de la TSA est absent chez les souris âgées dont la fonction hippocampique est altérée. Dans une dernière série d’expérience, l’analyse des effets d’une injection intra-hippocampique de TSA, après un apprentissage spatial, a permis de préciser les contributions respectives des histones H3/H4 et du facteur de transcription CREB dans les déficits mnésiques associés au vieillissement. Dans leur ensemble, nos travaux apportent des éléments importants concernant l’importance de l’acétylation des histones dans la modulation des interactions entre systèmes de mémoire hippocampique et striatal. / Post-translational modifications of histone proteins play a crucial role in regulating plasticity and memory-related gene expression. Among these modifications, histone acetylation leads to a relaxed or “opened” chromatin state, permissive for transcription. Our work aims to identify the role played by histone H3 and H4 acetylation in the formation of different forms of memory involving hippocampal and striatal systems in mice. We also examined whether alterations of histone acetylation are responsible for age-associated memory deficits. We used two versions of the Morris water maze learning task to dissociate a spatial form of memory that relies on the hippocampus and a procedural/cued memory supported by the striatum. Our results highlight a differential regulation of histone acetylation within the hippocampus and striatum depending on the nature of the task and age of animals. Spatial and cued learning elicited histone acetylation selectively in the hippocampus (CA1 region and dentate gyrus) and the striatum, respectively. Age-related spatial memory deficits were associated with opposite changes in H3 acetylation (increase) and H4 (decrease) selectively in the hippocampus. During a water maze competition task in which mice can choose between spatial and cue-guided strategies, intra-hippocampal injection of Trichostatin A (TSA), an histone deacetylase inhibitor, immediately post-acquisition, impaired striatal function and promoted the use of a hippocampus-based spatial strategy. However, this effect of TSA was absent in old mice in which hippocampal function is impaired. In a final series of experiments, analysis of the effects of intra-hippocampal TSA injection immediately after a spatial training helped to clarify the respective contributions of histone H3/H4 and the transcription factor CREB in spatial memory deficits associated with aging. Taken together, our work provides important information regarding the importance of histone acetylation in modulating interactions between hippocampal and striatal memory systems.