Made available in DSpace on 2014-12-17T15:37:21Z (GMT). No. of bitstreams: 1 FlavioFB.pdf: 284121 bytes, checksum: ff963989598b589fdee85c0d64ed36f6 (MD5) Previous issue date: 2007-04-13 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Several studies have shown that there is a circadian modulation of explicit memory. This modulation can occur independently in each one of the mnemonic processes. The aim of this study was to evaluate the influence of time of training on short-term memory (STM) and long-term memory (LTM), using a recognition task. Moreover, a possible circadian modulation in retrieving was investigated when this process matched the acquisition hour (time stamp). The chronotype variable was also considered. Fifty-seven undergraduate students aging between 18 and 25 years (21,72 ? 2,14; 28 ♂) participated in this study. In the training phase (acquisition) the subjects heard a ten word list. Following this, they answered a recognition test to evaluate STM and one week later they answered a recognition test to evaluate LTM. In each chronotype, the subjects were divided in groups according to the training hour, part of them in the morning and the other in the afternoon. One week later some of the subjects in each group underwent LTM testing in the morning and others in the afternoon. When the subjects performances were analyzed together, independently of the chronotypes, a training hour effect was found in the LTM. The subjects trained in the afternoon had better performance. No time of day effect was found in the STM and in retrieving from the LTM. However, the morning types who were trained and tested in the same hour had a better performance in the LTM when compared to morning types trained and tested in different hours. This effect did not occur when the other chronotypes were analyzed. The circadian modulation seems to occur at least in two different ways. First, there is a circadian modulation in the acquisition/consolidation processes, with a better performance occuring in the afternoon. Secondly, there is a modulation in the retrieval mnemonic process, called time stamp phenomenon. This phenomenon, that occurred in the morning types, is showed for the first time in humans / Na literatura h? diversas evid?ncias da modula??o circadiana na mem?ria expl?cita. Essa modula??o pode acontecer de forma independente em cada um dos processos mnem?nicos. O objetivo deste trabalho foi avaliar o efeito do hor?rio do dia sobre o desempenho da mem?ria de curto-prazo (MCP) e de longo-prazo (MLP), utilizando testes de reconhecimento de palavras. Al?m disso, foi investigada uma poss?vel modula??o na evoca??o quando esta ocorria no mesmo hor?rio da aquisi??o (estampa temporal), levando em considera??o a vari?vel cronotipo. Participaram do estudo 57 estudantes universit?rios, sendo 28 homens, entre 18 e 25 anos (21,72 ? 2,14). No treino (aquisi??o), os sujeitos escutaram uma lista de dez palavras. Logo a seguir, realizaram um teste de reconhecimento para avaliar a MCP e uma semana depois, realizaram um teste de reconhecimento para avaliar a MLP. Em cada um dos cronotipos, os sujeitos foram divididos em grupos conforme o hor?rio de realiza??o do treino da tarefa, parte pela manh? e a outra parte pela tarde. Uma semana depois parte dos sujeitos em cada um dos grupos realizou o teste para MLP pela manh? e outra pela tarde. Quando o desempenho dos sujeitos foi analisado conjuntamente, independente da classifica??o do cronotipo, foi encontrado um efeito do hor?rio da aprendizagem na MLP, tendo melhor desempenho os sujeito que foram treinados pela tarde. N?o foi evidenciado um efeito do hor?rio na MCP e na evoca??o da MLP. No entanto, os matutinos que foram treinados e testados no mesmo hor?rio tiveram um melhor desempenho do que os matutinos que foram treinados e testados em hor?rio diferentes. Esse fen?meno n?o foi encontrado nos outros cronotipos. A modula??o circadiana na mem?ria de reconhecimento parece ocorrer de pelo menos duas formas distintas. A primeira, no hor?rio da aquisi??o/consolida??o, tendo o hor?rio da tarde uma superioridade em rela??o ao da manh?. E a outra de acordo com o hor?rio em que ocorre a evoca??o (estampa temporal), tendo sido pela primeira vez demonstrado esse fen?meno em seres humanos, ainda que apenas nos matutinos

Developmental dyslexia is a specific reading and spelling disability with several explanatory proposals. Previous research has shown that there is a strong relation between developmental dyslexia and difficulties in phonological processing, which has resulted in the theory that the cause of developmental dyslexia is a specific weakness in phonological awareness. However, such a specific weakness does not explain the non-linguistic difficulties that are also common in developmental dyslexia. According to the Procedural Deficit Hypothesis (PDH), several (both linguistic and non-linguistic) difficulties that are observed in developmental dyslexia can be explained by abnormal development of the procedural memory system. Moreover, this hypothesis implies that the declarative memory system remains intact and may have a compensatory role for the reading disabilities in developmental dyslexia. In this study, the aspect of declarative memory that is visual recognition memory after incidental encoding was examined. 10 children with diagnosed developmental dyslexia and 10 typically developed children participated in the study. The results indicated an intact declarative memory in children with developmental dyslexia. However, no significant correlation between declarative memory and reading ability was found. Thus, the prediction that declarative memory can serve a compensatory role in developmental dyslexia was not supported. / Dyslexi är en specifik läs- och skrivsvårighet med flera förklaringsmodeller. Tidigare forskning har visat på ett starkt samband mellan dyslexi och svårigheter med fonologiskt processande, vilket har lett fram till hypotesen att orsaken till dyslexi är en specifik svaghet i fonologisk medvetenhet. En sådan specifik nedsättning kan dock inte förklara de icke-språkliga svårigheter som också är vanligt förekommande vid dyslexi. Enligt the procedural deficit hypothesis (PDH) kan många (både språkliga och icke-språkliga) svårigheter vid dyslexi förklaras av en nedsättning i det procedurella minnet. Vidare innebär hypotesen att det deklarativa minnet är intakt och kan fungera som kompensation för svårigheterna vid dyslexi. I denna studie undersöktes det deklarativa minnet i form av visuellt igenkänningsminne efter oavsiktlig inkodning. I studien deltog 10 barn med dyslexi och 10 barn utan dyslexi. Resultatet indikerade att det deklarativa minnet var intakt hos barnen med dyslexi. Däremot kunde inget signifikant samband mellan deklarativt minne och läsförmåga ses. Antagandet att deklarativt minne kan fungera som kompensation vid dyslexi kunde därför inte stödjas.

Dual-process models of recognition memory propose that recognition memory can be supported by either a general sense of familiarity or the recollection of the encoding context. One source of evidence supporting dual-process models comes from event-related potential (ERP) studies of recognition memory, which have identified distinct patterns of neural activity associated with familiarity and recollection (the mid frontal and left parietal old/new effects, respectively). In this thesis, dual-process accounts of recognition memory were investigated in a series of ERP studies using three categories of stimulus: previously unknown faces, famous faces, and names. For previously unknown faces, familiarity was associated with activity over posterior scalp electrodes while recollection was associated with topographically dissociable activity over anterior electrodes. These dissociable patterns of activity support dual-process models. However, the typical pattern of old/new effects was only observed for stimuli associated with pre-existing representations (i.e., names and famous faces), suggesting that the presence/absence of pre-existing representations may determine the particular retrieval processes that support recognition memory. Furthermore, recollection was associated with two different patterns of activity (anterior and left parietal effects), suggesting that recollection is not a homogenous process. Dual-process theories may represent an important starting point for investigating recognition memory, but neither familiarity nor recollection appear to be functionally homogenous processes when theorizing is constrained by the analysis of scalp recorded electrophysiological activity.

Les situations cliniques associant des troubles moteurs et une détérioration cognitive sont fréquentes et déroutantes pour le clinicien, qui est confronté à la difficile question du diagnostic différentiel entre plusieurs cadres nosographiques dont la maladie de Parkinson avec démence (MPD) et la démence à corps de Lewy Diffus (DCLD). Dans ce travail, nous avons étudié les caractéristiques neuropsychologiques pouvant différencier les deux affections. Nous avons, dans une première étude, montré que la mémoire de reconnaissance visuelle était altérée de façon différente. Dans un second travail, nous avons spécifié les caractéristiques de ces altérations en les rapprochant des classiques profils « cortical » et « sous cortical » de démence. Nous avons ainsi montré que la MPD présentait une altération de la mémoire de reconnaissance visuelle intermédiaire entre la Maladie d’Alzheimer et la DCLD. Enfin, dans une dernière partie, nous proposons des perspectives de recherche dans la continuité de ces travaux. / Clinical manifestations associating motor and cognitive impairment are frequently encountered and difficult for the clinician who is required to address the problem of making the correct differential diagnosis, particularly to differentiate Parkinson's disease with dementia (PDD) from Lewy bodies dementia (LBD). In this study, we examined the neuropsychological characteristics which allow us to differentiate the two disorders. In the first study, we demonstrated that visual recognition memory is disturbed differently in the two cases. In a second study, we specified the characterisstics of the modifications encountered by using the classic "cortical" and "subcortical" dementia profiles. We also showed that, in PDD, the alteration in visual recognition memory is intermediary between Alzheimer's disease and LBD. Finally, in the last part of our study, we suggest future avenues of research needed to complete our work.

The aim of this study is to investigate whether blind individuals display cognitive advantages over sighted individuals with regard to second language acquisition. Previous studies from neuropsychology have indicated that this is the case. It has been found that blind L1 speakers can compensate for loss of vision by developing better perceptual and cognitive skills compared to sighted individuals, skills that are highly relevant to language acquisition. These studies do not, however, investigate blind L2 speakers, for whom it is not clear whether these advantages are also found.  In all, 80 adults participated in the study: 40 L2 speakers of Swedish (11 early blind, 9 late blind, 20 sighted, AO<18) and a matching group and subgroups of L1 speakers. These speakers underwent tests on speech perception in noise, accentedness in an L2 and memory functions. The results revealed that L2 speakers are at a great disadvantage perceiving speech in noise compared to L1 speakers, and that there was no advantage associated with blindness. In the L1 speakers group, however, the results revealed that the early blind had advantages compared to the late blind and sighted in white noise, but that both blind groups were more negatively affected by babble noise than the sighted. The results in relation to accentedness in an L2 revealed that there were no advantages associated with blindness. The results further revealed there were no advantages associated with blindness on the episodic memory test. The results did, however, reveal that the early blind performed significantly better than the late blind and sighted on all phonological short-term memory tests and that both the early and late blind were significantly better than the sighted on recognition memory for new words, irrespective of language background. The conclusion is that blindness is associated with advantages in, for example, ability to learn new words and syntax, acquisition rate, ultimate L2 attainment, and language aptitude.

Utifrån the procedural deficit hypothesis (PDH) antas det deklarativa minnet vara intakt hos personer med dyslexi. Detta styrks av studier som visat att deklarativt minne är intakt eller förstärkt hos barn med SLI eller dyslexi då det undersökts med icke-språkliga minnestest. Personer med dyslexi som genomgår universitetsstudier antas kompensera för sina svårigheter på olika sätt, bland annat med det deklarativa minnet. I denna studie har deklarativt minne undersökts i form av visuellt igenkänningsminne efter oavsiktlig inkodning. Deltagarna utgjordes av 11 universitetsstuderande med dyslexi samt en kontrollgrupp på 26 universitetsstuderande utan dyslexi. Resultatet indikerade ett intakt deklarativt minne hos personer med dyslexi. En trend till att de även har ett förstärkt minne efter 24 timmar jämfört med kontrollgruppen kunde skönjas men var inte signifikant. Prediktionen att deklarativt minne används som kompensation i allmänhet samt för nedsatt läsförmåga kunde inte styrkas. Andra möjliga kompensatoriska strategier och förmågor än deklarativt minne diskuteras. / Based on the procedural deficit hypothesis (PDH) declarative memory is assumed to be intact in people with dyslexia. This is supported by studies showing that declarative memory is intact or enhanced in children with SLI or dyslexia when examined using non-verbal memory tests. People with dyslexia who undergo university studies are assumed to compensate for their difficulties in different ways, including with the use of declarative memory. This study examines the aspect of declarative memory that is visual recognition memory after incidental encoding. The participants were 11 university students with dyslexia and a control group of 26 university students without dyslexia. The results showed an intact declarative memory in people with dyslexia. A possible trend that they also have an enhanced memory after 24 hours compared with the control group could be seen but was not significant. The prediction that declarative memory is used as compensation in general and for impaired reading skills could not be substantiated. Other possible compensatory strategies and abilities besides declarative memory are discussed.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Traumatic brain injury (TBI) is a major cause of death and disability. This condition results in neurological and cognitive impairment. In this context, it has been demonstrated that bradykinin, the main metabolite of the kallikrein-kinins system is involved in the increased permeability of the blood-brain barrier, in edema formation and leukocyte accumulation induced by TBI. Experimental findings also indicate an connection between kinin receptors and the activity of the enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, an enzyme that produces superoxide radical. It is known that the kalikrein-kinin and NADPH-oxidase activity participate of neuroinflammation triggered by TBI. However, few studies have evaluated their effects on the development of posttraumatic cognitive impairment. Hence, the present study evaluated the role of kinin receptors (B1 and B2) and the NADPH-oxidase inhibitor (apocynin)in neuromotor deficits, memory impairment, cortical lesion volume, oxidative and inflammatory damage induced by moderate lateral fluid percussion injury in mice. Therefore, we determined the effects of kinin receptors antagonists (des - Arg9-[Leu8]-bradykinin and HOE-140) and apocynin injected subcutaneously 30 min 24 hours post trauma. The present study demonstrated that both, HOE-140 and apocynin, protected against memory impairment triggered by trauma, but showed no effects in motor dysfunction caused by TBI. It should be noted that memory improvements was not due to nonspecific effects over the memory test, because the pharmacological treatment used in this study did no alter locomotor and/or anxiety-like behavioral. Treatment with HOE-140 also attenuated the NADPH-oxidase activity, reinforcing the connection between the B2 receptor and this enzyme. Moreover, both treatments attenuated the ipsilateral cortex inflammation (levels of interleukin-1β, tumoral necrosis factor-α and nitric oxide metabolites) and oxidative damage (lipid peroxidation, protein carbonylation and inhibition of Na+, K+ ATPase) induced by tested model. On the other hand, only treatment with HOE-140 reduced the cerebral edema. The results presented in this study suggest that kinins, through of the B2 receptor and possibly through NADPH-oxidase, are involved in neuroinflammation and oxidative stress caused by trauma. Moreover, it is plausible that excessive activation of B2 receptors and subsequent activation of the enzyme NADPH-oxidase facilitate the cortical lesion progression resulting in deterioration of object recognition memory. / O traumatismo crânio encefálico (TCE) é uma das maiores causas de morte e de incapacitação, resultando frequentemente em disfunções neurológicas e prejuízo cognitivo. Neste contexto, tem sido demonstrado que a bradicinina, o principal metabólito do sistema calicreína-cininas, está envolvida no aumento da permeabilidade da barreira hematoencefálica, na formação de edema e no acúmulo de leucócitos induzidos pelo TCE. Achados experimentais também indicam uma interconexão entre os receptores das cininas e a atividade da enzima Nicotinamida Adenina Dinucleotídeo Fosfato (NADPH)-oxidase. Esta enzima é uma conhecida produtora de radical superóxido e também parece estar envolvida na toxicidade induzida pelo TCE. Embora se conheça o envolvimento do sistema calicreína-cininas e da atividade da NADPH-oxidase na neuroinflamação desencadeada pelo TCE, poucos trabalhos têm avaliado seus efeitos no desenvolvimento do déficit cognitivo pós-traumático. Diante disto, o presente estudo avaliou o papel dos receptores das cininas (B1 e B2) e da apocinina (um inibidor da NADPH-oxidase) nos déficits neuromotor e de memória, bem como no volume de lesão cortical e nas alterações oxidativas e inflamatórias induzidas pelo modelo de lesão cerebral moderada por percussão de fluido lateral em camundongos. Para tanto, avaliou-se os efeitos dos antagonistas dos receptores das cininas dos subtipos B1 (des-Arg9-[Leu8]-bradicinina) e B2 (HOE-140) e da apocinina, injetados subcutaneamente 30 min e 24 horas após o trauma. O presente estudo demonstrou que tanto o HOE-140, como a apocinina protegeram contra o prejuízo de memória desencadeado pelo trauma, mas não apresentaram efeitos estatisticamente significantes sobre a disfunção motora. Cabe salientar que os testes de ansiedade e locomoção indicam que a melhora de memória alcançada com os tratamentos não se devem a interferências inespecíficas sobre a execução do teste de memória. O tratamento com HOE-140 atenuou ainda a atividade da NADPH-oxidase, reforçando a interconexão entre o receptor B2 e a enzima. Além disso, ambos os tratamentos foram eficazes em atenuar, em córtex ipsilateral, os parâmetros inflamatórios (níveis de interleucina-1β, fator de necrose tumoral-α e de metabólitos do óxido nítrico) e o dano oxidativo (lipoperoxidação, carbonilação proteica e inibição da Na+, K+ATPase) induzidos pelo modelo estudado. Por outro lado, apenas o tratamento com HOE-140 obteve uma redução estatisticamente significante sobre o edema cerebral. Os resultados apresentados permitem concluir que as cininas, por ação do receptor B2 e possivelmente da NADPH oxidase, estão envolvidas na neuroinflamação e no estresse oxidativo. Além disso, é plausível que a excessiva ativação dos receptores B2 seguida da ativação da enzima NADPH-oxidase facilite a progressão da lesão cortical repercutindo, desta forma, na deterioração da memória de reconhecimento de objetos.

Made available in DSpace on 2014-12-17T15:36:43Z (GMT). No. of bitstreams: 1 FernandoRFS_TESE.pdf: 469950 bytes, checksum: a8f86cc336421fd74e299ebe8f8d1daf (MD5) Previous issue date: 2014-11-04 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The use and the demand for substances that enhance masculinity, strength and sexual power are not novel. Over the years, this search has assisted the research directions in this area, leading to the discovery of the primary male sex hormone testosterone in 1935. Since then, numerous testosterone analogue compounds were synthesized, which are generically called Anabolic Androgenic Steroids (AAS). The AAS were produced for therapeutic purposes, but an increase in the use of these compounds for other purposes occurred over time. Initially they were used mainly to improve performance in athletes. However, recent studies have shown that the use of AAS by non-athletes with aesthetical purposes have been increasing as well. The abuse of AAS with non-clinical purposes can promote a number of physiological alterations, such as heart, liver, respiratory and psychological problems such as changes in mood, levels of anxiety and aggression. Exposure to supraphysiological doses of AAS is associated with behavioral changes, however, little is known about the effects of AAS on cognitive functions. In this work, we aimed to mimic the AAS abuse in humans with intramuscular administration of a supraphysiological dose of testosterone propionate (TP) in rats. We investigated the effects of this treatment on different aspects of cognitive function, specifically learning, memory and anxiety. Adult male Wistar rats were tested in the spontaneous alternation, novel object recognition and plus-maze discriminative avoidance tasks. The control group received intramuscular injections of vegetable oil (vehicle), and the TP group received injections of TP (10 mg/kg, i.m.). The injections were administered for 40 days, with intervals of 48 hours (chronic treatment) or in a single injection (acute treatment). In addition to the behavioral assessments, we performed biochemical analyzes as indicators of the endocrine effects of the treatment. Our results show that chronic treatment with a supraphysiological dose of TP caused memory impairments in the novel object recognition and the discriminative avoidance tasks. The spatial working memory (evaluated by spontaneous alternation task) was not affected. Also, we did not observe changes in anxiety levels. Regarding the biochemical parameters, chronic treatment increased serum levels of glutamicpyruvic transaminase, an indicator of hepatic and pancreatic lesions (as those observed after chronic use of these substances in humans). On the other hand, acute treatment with PT did not promote significant changes in any of these parameters when compared to the control group. In summary, we conclude that chronic treatment with a supraphysiological dose of testosterone propionate produces memory deficits in novel object recognition and retrieval of the discriminative avoidance task in adult male rats / A utiliza??o e a busca por subst?ncias que aumentem a masculinidade, a for?a e a pot?ncia sexual n?o ? recente. Com o tempo, essa busca auxiliou no direcionamento de pesquisas na ?rea, levando a descoberta do principal horm?nio masculino a testosterona em meados da d?cada de 30. A partir desse momento, in?meros compostos foram sintetizados com o intuito de mimetizar os efeitos deste horm?nio, aos quais hoje chamamos genericamente de Esteroides Anab?licos Androg?nicos (EAA). A princ?pio, esses EAA foram sendo produzidos com prop?sitos terap?uticos. No entanto, iniciou-se o uso crescente desses compostos com outras finalidades, principalmente para a melhoria de desempenho em atletas. Al?m disso, estudos recentes t?m demonstrado que os EAA est?o sendo cada vez mais utilizados por n?o atletas, por indiv?duos que n?o s?o atletas, mas, buscam um corpo esteticamente perfeito. Paralelamente, o crescente abuso dos EAA com finalidades n?o cl?nicas pode promover uma s?rie de altera??es fisiol?gicas nocivas, tais como problemas card?acos, hep?ticos, respirat?rios e tamb?m psicol?gicos como altera??es de humor, nos n?veis de ansiedade e na agressividade. A exposi??o a doses suprafisiol?gicas de EAA est? associada com altera??es comportamentais, contudo, pouco se sabe sobre os efeitos dos EAAs sobre as fun??es cognitivas. Neste trabalho, mimetizamos o abuso de EAA em humanos atrav?s da administra??o intramuscular de uma dose suprafisiol?gica de propionato de testosterona (PT), em ratos, com o objetivo de investigar os efeitos desse tratamento sobre diferentes aspectos das fun??es cognitivas, especialmente aprendizado, mem?ria e ansiedade. Ratos Wistar machos adultos foram submetidos aos testes de alterna??o espont?nea, reconhecimento de objetos e esquiva discriminativa em labirinto em cruz elevado. O grupo controle recebeu inje??es intramusculares de ?leo vegetal (ve?culo); e o grupo testosterona recebeu inje??es de PT (10 mg/kg, i.m.). As inje??es foram administradas por 40 dias, com intervalos de 48 horas (tratamento cr?nico) ou em uma ?nica inje??o (tratamento agudo). Al?m das avalia??es comportamentais, foram realizadas an?lises bioqu?micas como indicadores dos efeitos end?crinos do tratamento. Nossos resultados mostram que o tratamento cr?nico com uma dose suprafisiol?gica de PT acarretou preju?zos na mem?ria de reconhecimento de objetos novos e na evoca??o da tarefa da esquiva discriminativa. A mem?ria espacial operacional (avaliada pelo teste de alterna??o espont?nea) n?o foi afetada bem como n?o observamos altera??es nos n?veis de ansiedade. Em rela??o aos par?metros bioqu?micos avaliados, o tratamento cr?nico elevou os n?veis s?ricos da transaminase glut?mica pir?vica (TGP), um indicador da presen?a de les?es hep?ticas e pancre?ticas (assim como as observadas ap?s o uso cr?nico dessas subst?ncias em humanos). Por outro lado, o tratamento agudo com PT n?o promoveu altera??o significativa em nenhum dos par?metros avaliados, quando comparados ao grupo controle. Em s?ntese, podemos concluir que o tratamento cr?nico com uma dose suprafisiol?gica de testosterona produz d?ficits de mem?ria de reconhecimento de objetos bem como preju?zos na mem?ria na tarefa da esquiva discriminativa em ratos machos adultos

L’objectif de ce travail de thèse était d’évaluer l’état des processus de récupération en mémoire dans la maladie d’Alzheimer afin de développer des programmes de prise en charge cognitive novateurs. Les deux premières études ont porté sur la caractérisation de ces processus à travers l’évaluation des performances de patients avec une maladie d’Alzheimer à des tâches de reconnaissance mnésique. Les deux études suivantes se sont intéressées au développement de programmes d’intervention cognitive ayant pour objectif de réduire les troubles cognitifs et leur retentissement, l’un en améliorant les processus cognitifs altérés à partir d’un entraînement cognitif appliquant la répétition-lag procédure et l’autre, en sollicitant les processus cognitifs préservés à partir d’un apprentissage par des techniques de réhabilitation cognitive, à recourir à l’utilisation d’aides externes. Les résultats ont mis en évidence une détérioration sélective des processus de reconnaissance chez les patients à un stade léger de la maladie ; la recollection serait particulièrement altérée alors que la familiarité resterait préservée. De plus, le déficit des capacités de reconnaissance de la source serait lié à l’altération des processus stratégiques de reconnaissance de la source, les processus associatifs resteraient préservés. Ensuite, le programme d’entraînement cognitif expérimental s’est révélé efficace, des gains cognitifs ont été objectivés à des tâches cognitives de transfert. De même, le programme de réhabilitation cognitive par le biais d’un apprentissage combinant les techniques de la récupération espacée et de l’apprentissage sans erreur a permis de réduire l’impact des troubles cognitifs dans la vie quotidienne / The main objective of this thesis was to evaluate retrieval memory processes in Alzheimer’s disease in order to develop innovative cognitive interventions. The first two studies focused on the characterization of these processes through performance evaluation of patients with Alzheimer’s disease in recognition memory tasks. The next two studies became interested in development of cognitive intervention programs aimed at reducing cognitive impairment and their impact. One tries to improve impaired cognitive processes from a cognitive training using the repetition-lag procedure and the other one uses different cognitive rehabilitation techniques that involve preserved cognitive processes to learn to resort to the use of external aids. The results showed a selective deficit in recognition processes in patients with a mild stage of Alzheimer’s disease, recollection would be particularly affected as familiarity remains preserved. In addition, source recognition deficit could be explained by a specific alteration of source recognition strategic processes whereas associative processes should remain preserved. Secondly, the experimental cognitive training program was effective, cognitive gains were objectified in transfer tasks. Similarly, the cognitive rehabilitation program using spaced retrieval technique and errorless learning has reduced the impact of cognitive impairment in everyday life

O paradigma intruso-residente vem sendo intensamente empregado em estudos para avaliar a memória de reconhecimento social em roedores. Tipicamente, ratos adultos, denominados residentes, são expostos a dois encontros sucessivos, de 5 minutos cada, com um mesmo rato juvenil ou com ratos juvenis diferentes, denominados intrusos; o intervalo de tempo entre encontros é 30 minutos. A quantidade de comportamentos sociais do residente (no segundo encontro) em relação a um intruso familiar é substancialmente menor do que o observado no primeiro encontro, o que não ocorre quando o segundo encontro envolve um juvenil novo; esse resultado caracteriza a memoria de reconhecimento social. Se o intervalo de tempo entre os encontros é aumentado para 60 minutos, a redução da investigação social do intruso familiar por parte do residente desaparece, levando à conclusão de que a memória de reconhecimento social seria um mecanismo para retenção temporária de informações. O objetivo central do presente trabalho foi contribuir para o entendimento da memória de reconhecimento social em ratos. Foram realizados três experimentos. No primeiro experimento avaliou-se se a expressão de comportamentos sociais e também da memória de reconhecimento social estão sujeitos à modulação temporal. No segundo experimento avaliou-se em que extensão o aumento do tempo de exposição ao intruso durante o primeiro encontro resulta num aumento da duração da memoria de reconhecimento social. No terceiro experimento avaliou-se se um procedimento de rotina na maioria dos laboratorios, o transporte dos animais da sala de experimentos para o biotério, interfere na memória de reconhecimento social, quando realizado 0,5 ou 6 horas após o primeiro encontro. Os resultados mostraram que (1) a expressão de comportamentos sociais e a memória de reconhecimento social estão sujeitos à modulação temporal, sendo mais intensos quando os testes são realizados na fase inativa (Capítulo 2), de modo que este fator deve ser levado em consideração quando do planejamento de experimentos envolvendo sociabilidade, (2) o aumento da duração do primeiro encontro para 2 horas ou mais revelou uma memória de reconhecimento social que dura pelo menos 24 horas (Capítulo 3), permitindo questionar que se trate de um dispositivo de curta duração, e (3) o transporte dos animais para o biotério 0,5 horas, mas não 6 horas, depois do primeiro encontro, prejudica a memória de reconhecimento social (Capítulo 4), indicando que se deve estar atento às rotinas laboratoriais pois as mesmas podem interferir no desempenho dos animais em testes de memória. Em associação com essas relevantes observações experimentais, foram propostas estratégias de análise dos dados gerados com esse tipo de experimentação e também discussões conceituais sobre a caracterização da memória de reconhecimento social, que contribuem marcadamente para essa área de estudos. / The intruder-resident paradigm has been extensively employed in studies of social recognition memory in rodents. Typically, adult rats, named residents, are exposed to two 5-min successive encounters with the same juvenile intruder or with two different juveniles; the time interval between the encounters is 30 min. The amount of social behaviors exhibited by the resident rats towards the same intruder juvenile in the second encounter is substantially smaller when compared to both that seen in the first encounter and that seen towards a different juvenile; these results characterize social recognition memory. When the time interval between encounters is increased to 60 min, that reduction of the investigation towards the familiar juvenile intruder vanishes, which is seen as evidence that social recognition memory corresponds to a short-term memory mechanism. The aim of this study was to contribute for our understanding of social recognition memory in rats. Three experiments were run. The first experiment evaluated to which extent both social behaviors and social recognition memory are influenced by temporal phase effects. The second experiment evaluated to which extent the increase in the duration of the first encounter renders social recognition memory longer. The third experiment evaluated to which extent the transportation of the resident rats from the experimental room to the animal facilities either 0.5 or 6 hours after the first encounter, interferes with social recognition memory. The results showed that (1) the expression of social behaviors and of the social recognition memory are modulated temporal phase effects, being stronger when animals are tested in their inactive phase (Chapter 2); thus, this aspect has to be considered in studies on sociability, (2) the increase of the first encounter duration for 2 hours or longer renders social recognition memory to last at least 24 hours (Chapter 3); this allows to question that social recognition memory corresponds to a short-term memory mechanism, and (3) transportation of the resident rats to the animal facilities 0.5, but not 6 hours, after the end of the first encounter disrupts social recognition memory (Chapter 4), indicating that one has to be cautious about usual laboratory routines, because they may interfere with performance of the memory tasks when executed a short time after training the animals.Associated with these relevant experimental observations, these studies allowed proposing novel strategies for data analysis and discussing conceptual issues about the characterization of social recognition memory that give a substantial contribution for this area.