Submitted by Maicon Juliano Schmidt (maicons) on 2015-04-15T18:41:58Z No. of bitstreams: 1 Edilson Pastore.pdf: 1708498 bytes, checksum: cb7f365a867bba996d379bf77353991f (MD5) / Made available in DSpace on 2015-04-15T18:41:58Z (GMT). No. of bitstreams: 1 Edilson Pastore.pdf: 1708498 bytes, checksum: cb7f365a867bba996d379bf77353991f (MD5) Previous issue date: 2012-01-31 / Nenhuma / A presente dissertação de Mestrado investigou o desempenho cognitivo de participantes com Transtorno de Personalidade Borderline (TPB) com e sem histórico de tentativas de suicídio. A apresentação da revisão de literatura e dos resultados empíricos deste trabalho foi descrita em um artigo teórico e um artigo empírico sobre o TPB, suicídio e funções cognitivas. Primeiramente, apresenta-se o artigo teórico, que traz uma revisão assistemática e crítica da literatura sobre o transtorno, abordando as particularidades do desenvolvimento dessa patologia e discutindo sobre os aspectos cognitivos. Essa revisão teve como foco as funções executivas, especialmente: atenção, concentração, tomada de decisões, organização do pensamento e memória operacional, sugerindo que déficits nessas funções podem ser fatores de risco para o suicídio em pacientes com esse diagnóstico. As conclusões do artigo teórico apontam para a existência de déficits específicos na cognição, especialmente na área de execução em participantes com diagnóstico de TPB. Discutiram-se artigos atuais encontrados sobre a temática e problematizou-se a necessidade e relevância de investigações e achados dessa natureza. O artigo empírico apresenta os resultados de uma pesquisa quantitativa, transversal e de comparação entre grupos realizada com uma amostra de 82 pacientes (M=31,80; DP=0,96) diagnosticados com TPB internados em uma clínica psiquiátrica de Porto Alegre, Rio Grande do Sul, Brasil. Foi aplicada a Escala Wechsler de inteligência para adultos (WAIS III), a Escala Barratt de Impulsividade, a Escala Beck de Suicídio e a Escala FAST, além de um questionário contendo dados sociodemográficos. Não foi encontrada diferença significativa em termos de QI total entre os participantes com TPB com e sem histórico de tentativas de suicídio, indicando assim que a heterogeneidade dos pacientes que apresentam esse diagnóstico, assim como o grande número de comorbidades apresentadas por essa população, podem ter sido fatores importantes para explicar esse resultado. Entretanto, verificou-se que pacientes com histórico de tentativas de suicídio apresentam índice de impulsividade mais elevado, especialmente abaixo de 30 anos de idade, o que salienta que nesta idade pacientes com TPB podem ser mais vulneráveis tanto para tentativas de suicídio quanto para sua efetivação. Embora não se tenha encontrado diferença significativa entre os grupos, as médias na Escala Wechsler (funções cognitivas) quanto ao QI total situaram-se dentro do nível médio de funcionamento cognitivo com QI de 92,73 (DP=14,39) para o grupo dos pacientes com histórico de tentativa de suicídio e 96,06 (DP=17,8) para o grupo sem tentativas de suicídio. Os níveis de impulsividade foram maiores no grupo de pacientes com histórico de tentativas de suicídio, assim como o grau de adaptação medido pela Escala FAST se mostrou mais prejudicado no mesmo grupo. Os resultados desta dissertação elucidam aspectos sobre o TPB e permitem refletir sobre adequadas formas de tratamento. Fica também evidenciada a necessidade da realização de outros estudos dentro dessa mesma temática, em virtude da carência de pesquisas neuropsicológicas ou sobre funções cognitivas em pacientes com diagnóstico de TPB no Brasil. / The objective of the present Master's thesis was to investigate the cognitive performance of participants with Borderline Personality Disorder (BPD) with and without a history of suicide attempts. The review of the literature and the empirical results of this study were described in a theoretical article and an empirical article about BPD, suicide, and cognitive functions. The theoretical article consisted of an asystematic and critical review of the literature on the disorder, addressing the characteristics of the development of this pathology and discussing its cognitive aspects. This review of the literature focused on executive functions, especially: attention, concentration, decision making, organization of thought, and working memory, suggesting that deficits in these functions may be risk factors for suicide in patients with this diagnosis. The conclusions of the theoretical article indicate the presence of specific cognition deficits, mainly in the executive functions of the participants diagnosed with BPD. We discussed recent articles on the topic and approached the need and relevance of further studies and similar findings. The empirical article presents the results of a quantitative, cross-sectional and comparative study conducted with a sample of 82 patients (M=31.80, SD=0.96) diagnosed with BPD and admitted to a psychiatric clinic in Porto Alegre, Rio Grande do Sul, Brazil. The Wechsler Adult Intelligence Scale (WAIS III), the Barratt Impulsiveness Scale, the Beck Suicide Scale, the FAST scale, and a questionnaire containing sociodemographic data were administered to the participants. There was no significant difference in terms of total IQ among the participants with BPD with and without a history of suicide attempts, suggesting that the heterogeneity of patients with this diagnosis, as well as the large number of comorbidities in this population, may have been important factors to explain this result. However, we found that patients with a history of suicide attempts have higher index of impulsivity, especially patients younger than 30 years, leading to the conclusion that individuals of this age group with BPD may be more vulnerable to both suicide and suicide attempts. Although there was no significant difference between the groups, the means on the Wechsler Scale (cognitive functions) in terms of total IQ were within the mean level of cognitive functioning with an IQ of 92 for the group of patients with a history of suicide attempt and 96 for the group without suicide attempts. Levels of impulsivity were higher in patients with a history of suicide attempts; in addition, the degree of adaptation measured by the FAST Scale was lower in the same group. These results explain aspects of BPD and provide the opportunity of developing appropriate therapeutic methods. The need for further studies on this topic was also evidenced by the lack of neuropsychological research or studies on cognitive functions in patients diagnosed with BPD in Brazil.

Dans un environnement en constant changement, les fonctions exécutives (FRE) nous permettent d'organiser l'information en provenance de sources multiples, de s'adapter à des situations sociales complexes et d'inhiber les comportements inappropriés. Les recherches sur le fonctionnement exécutif ont été initiées en neuropsychologie, après avoir observé chez des patients frontaux, des difficultés à organiser leurs comportements quotidiens sans pour autant présenter de difficultés de langage ou de mémoire. Un grand nombre de tests neuropsychologiques sont disponibles afin d'évaluer les FE. Cependant, ces tests sont souvent critiqués pour leur complexité et leur manque de validité de construction. Le champ des FE manque en réalité de modèles théoriques précis qui permettraient de décrire ces fonctions et leurs potentielles interactions pour le contrôle des comportements complexes. En conséquence, les tâches sont souvent construites de manière intuitive, dans le présent travail de thèse, après revue d'un état de l'art sur les FE (Ch1), je propose une nouvelle tâche, le spatial-tapping, qui pourrait être utilisée en remplacement des tâches classiques complexes (Ch2). Je promeus également le potentiel de cette tâche à être utilisée dans des contextes cliniques (Ch3). Je présente finalement comment les analyses réalisées pour le spatial-tapping afin d'étudier les FE peuvent être transférées à des situations motrices plus complexes, comme la coordination bi-manuelle (Ch4). En conclusion, les résultats présentés dans ce travail de thèse sont en faveur de l'idée selon laquelle notre organisation mentale reflète la manière dont on organise nos mouvements. / In a constant changing environment, executive abilities allow us to organize sensory information of multiple sources and to adapt to diverse stuations while at the same time inhibiting inappropriate behaviors. research on the executive functions (EFS) have historical roots on neuropsychology, with the description of frontal patients that were showing disruptions in organizing their daily behaviors independently of any impairment in memory, language or general intelligence. A wide range of neuropsychological tools is used today to evaluate executive abilities : tower of London for planning, go-no-go for inhibition, etc. However, the classical tasks often present methodological limitations and they lack of correpondence between process and behavior. Furthermore, the field lacks of a compelling theory that make links between the EFS themselves. The present PHD work was an attempt to propose a novel task to assess the EFS in the place of the classical batteries of neuropsychological tasks. After offering an overview of the EF literature and presenting simple motor tasks that seem to target similar EFS than those described in neuropsychology (Ch1), I present the spatial-tapping task as a challenging paradigm to understand the relationships between the different EFS (Ch2), and its potential to be used in clinical settings (Ch3). The I present how a similar approach can be used to investigate how EFS intervenes in the control of more complex motor sequences, E.G. bi-manual tasks (Ch4). Overall, the results presented here support an emboided perspective of cognition with mental organization reflecting the way one plans motor sequences for adaptive behavior.

L’objectif général de cette thèse est d’étudier la production quantitative (i.e., nombre de mots) et qualitative (i.e. regroupements et alternances) du verbe d’action dans le vieillissement normal et dans les pathologies du mouvement à travers la tâche de fluence d’action, comparativement aux fluences classiques (i.e., sémantique et littérale). Nous avons montré que la production lors d’une tâche de fluence d’action est altérée chez des adultes âgés (60 ans et plus) comparativement à des adultes jeunes (30 ans et moins) et qu’elle est en lien avec les fonctions exécutives (Expérience 1) et la mémoire de travail (Expérience 3) chez l’adulte âgé. L’effet de l’âge paraît être modifié par le temps de production, les adultes âgés produisant moins de verbes d’action que les adultes jeunes pour un temps de trois minutes (Expérience 1) mais pas pour des temps d’une (Expérience 2) et de deux minutes (Expérience 3). De plus, les adultes âgés prenaient davantage en considération la consigne temporelle lors des tâches de fluence verbale que les adultes jeunes (Expérience 2). Les données d’une tâche d’association verbale (Expérience 4) indiquaient que les associations entre les noms et les verbes sont modifiées par l’âge. Nous avons comparés les performances de patients atteints de pathologiesdu mouvement à celles de participants contrôles lors de la tâche de fluence d’action. Nous avons montré que la production quantitative lors cette tâche est altérée chez des patients atteints de maladie de Parkinson (Expérience 5) et d’atrophie multisystématisée (Expérience 6). Dans le tremblement essentiel (Expérience 7), nous avons montré une atteinte de la fluence d’action alors que le traitement des verbes, lors d’une tâche de décision lexicale, n’était pas altéré. De plus, la chirurgie (stimulation cérébrale profonde) modifiait qualitativement la production dans la tâche de fluence d’action. Nos données montrent un impact du vieillissement normal et des pathologies du mouvement sur la production du verbe d’action, enraison de la nature fortement exécutive de ce processus. / The aim of this thesis is to investigate the production of action verbs through the action fluency task, in comparison to classical fluency tasks (i.e., semantic and letter). In first instance, production has been studied, both quantitatively and qualitatively, in aging. We have shown that action fluency is impacted by healthy aging and is related to executive functions (Experiment 1) and working memory (Experiment 3) in older adults. This effect of age appearsto be affected by production time, with older adults producing fewer action verbs than younger adults in three minutes (Experiment 1) but not in one (Experiment 2) and two minutes (Experiment 3). In addition, older adults took more into account the time instruction during verbal fluency tasks (Experiment 2). The verbal association task’s data (Experiment 4) indicated that associations between nouns and verbs are modified by age. In second instance,the production of action verbs has been studied within movement disorders. We have shown that the production in the action fluency task and the adaptation to time instruction are impacted by Parkinson's disease (Experiment 5). We have also shown that action fluency is altered within an atypical parkinsonism, multiple system atrophy (Experiment 6). In essential tremor (Experiment 7), we have shown an impairment of action fluency while verbs treatment, in a lexical decision task, was not altered. In addition, surgery (deep brain stimulation) qualitatively modified the production of verbs in action fluency. Our data highlight the impact of healthy aging and movement disorders on the production of action verb, due to the highly executive nature of this process.

En raison du risque de perturbation des fonctions exécutives (FE), les recommandations médicales préconisent un suivi systématique du développement neuropsychologique des enfants atteints de phénylcétonurie, diagnostiqués et traités précocement (PCU-TP). En revanche, des divergences existent quant aux modalités pratiques d’évaluation. Ce travail de thèse a pour objectif d’interroger la pertinence de différents outils d’évaluation des FE en regard de la compréhension du phénotype neuropsychologique de ces enfants. Il s’agit d’apporter des préconisations d'évaluation puis de les confronter aux recommandations actuellement en vigueur. Dans ce contexte, 31 enfants PCU-TP ont été évalués à l’aide de tâches exécutives basées sur la performance et d’un questionnaire évaluant les comportements exécutifs à la maison et à l'école. Les résultats confirment la présence de difficultés exécutives par rapport à des enfants contrôles. Les difficultés décrites par l'entourage semblent majorées en regard des troubles observés aux tâches, suggérant que ces deux types d’outil évaluent des aspects exécutifs différents. Ce travail incite à préconiser l’utilisation d’outils variés et complémentaires et justifie la pertinence d’une évaluation plurielle et exhaustive des différentes composantes exécutives.Reste le problème majeur des outils actuellement disponibles. Dans cette perspective, la dynamique pluridisciplinaire associant cliniciens et universitaires est à encourager afin de proposer des outils fiables, permettant une évaluation puis une prise en charge au plus près des difficultés des patients. / Due to the risk of the impairment of Executive functions (EF), medical recommendations advocate asystematic follow up of the neuropsychological development for children with early and continuously treated phenylketonuria (ECT-PKU). However, there are discrepancies in the practical modalities of evaluation.This thesis is looking to question the relevance of the different evaluation tools for the EF with regards to the understanding of these children’s neuropsychological phenotype. It is about bringing evaluation recommendations and comparing them with the current guidelines. In this context, thirty one children with ECTPKU have been evaluated with executive tasks based on performance, and with a questionnaire assessing everyday executive functioning at home and at school.The results confirm some executive difficulties compared to control children. The difficulties described by the parents and teachers seem to be increased in relation to the disorders observed during the tasks. This suggests that these two types of tools evaluate different executive aspects. This work recommends the use of varied and complementary tools and it justifies the relevance of a plural and exhaustive evaluation of the different executive components. The major issue of the tools currently available remains. In this perspective, the pluridisciplinary dynamic associating clinicians and scholars is to be encouraged in order to offer reliable tools and thus allowing an evaluation, and a care and support, that are closer and more appropriate to the patient's difficulties.

L’objectif de cette thèse était d’étudier les fonctions exécutives dans la maladie de Parkinson et leurs implications dans la conduite automobile. Nous avons mesuré séparément les fonctions de flexibilité mentale et de mise à jour par des tests neuropsychologiques et des tâches sur simulateur de conduite. Nous avons fait l’hypothèse que ces fonctions étaient plus altérées chez les patients et que leurs déficits influençaient la performance de conduite. Trois études ont été réalisées : les deux premières sur simulateur et la dernière sur route avec un véhicule instrumenté. Les résultats de la première étude ont montré un déficit de la fonction de mise à jour chez les patients par rapport aux contrôles. La deuxième étude consistait à tester une seconde fois les conducteurs deux ans après la première étude. En deux ans, la fonction de flexibilité s’est dégradée chez les patients, suggérant que les deux fonctions étudiées ont évolué différemment : la mise à jour étant atteinte plus précocement dans la maladie. Les patients déclaraient également avoir restreint leur conduite. Les résultats de la troisième étude sur route ont permis d’identifier les conducteurs parkinsoniens à « risque » d'être dangereux, i.e. ceux ayant le plus de difficultés en conduite (évaluation conjointe de l’expérimentateur et du moniteur d’auto-école). Les conducteurs à « risque » avaient des performances plus faibles aux tests de mise à jour et de flexiblité par rapport aux conducteurs parkinsoniens sécuritaires. L’ensemble de ces travaux mettent en évidence le rôle essentiel de la mise à jour et de la flexibilité mentale dans la conduite automobile chez des personnes atteintes de la maladie de Parkinson. / The objective of this thesis was to investigate executive functions in Parkinson’s disease and their implications on driving. We have chosen to separately assess mental flexibility and updating information in working memory by neuropsychological tests and driving simulator tasks. We tested the hypothesis that these two executive functions were impaired in patients and that their deficits influenced the driving performance. Three studies were realised: the first two used the driving simulator and the last was performed on-road with an instrumented vehicle. Results of the first study have shown an updating impairment in patients compared to controls. The second study consisted of assessing the drivers a second time two years after the first study. In two years, the flexibility function declined in patients, suggesting that the two selected functions did not change in a similar way: updating is affected earlier in the disease than mental flexibility. Also, patients declared to have restricted their driving. Results of the third on-road study allowed us to identify “at-risk” drivers with Parkinson’s disease, that is to say those having the most driving difficulties (assessment from both experimenter and a driving instructor). At-risk drivers had poorer performances in updating and flexibility tasks compared to “safe” drivers. All of these studies emphasised the essential role of updating and mental flexibility in driving in people with Parkinson’s disease.

L'inhibition de réponse joue un rôle majeur dans le contrôle cognitif. Mais les relations entre activité cérébrale et comportement sont particulièrement difficiles à appréhender puisque la fonction est précisément destinée à prévenir tout comportement observable… Dans une première partie, nous proposons une revue de questions mettant en évidence la nécessité d'utiliser des méthodes psychophysiques adaptées. Nous proposons également une analyse systémique des travaux utilisant l'électroencéphalographie, méthode largement privilégiée pour sonder la dynamique des mécanismes inhibiteurs. Dans une seconde partie, nous mettons en œuvre ces propositions dans le cadre d'une étude combinée EEG/IRMf. Grâce à des méthodes avancées de traitement du signal EEG, nous suggérons la mise en jeu de mécanismes automatiques, non sélectifs, d'inhibition de réponse dès lors que le contexte événementiel est incertain. Il reposerait sur la pré-activation d'une circuiterie auto-inhibitrice dans le complexe moteur supplémentaire, implémenté par un large réseau médial frontopariétal. Dans les troisième et quatrième parties, nous montrons le rôle majeur de cette fonction dans d'autres processus cognitifs et illustrons les conséquences cliniques de son dysfonctionnement. Nous montrons en particulier que l'impulsivité n'est pas la seule expression des troubles du contrôle inhibiteur. La difficulté à initier une action constituerait, dans la maladie de Parkinson, une conséquence directe de ce dysfonctionnement. L'implication d'une dérégulation du système noradrénergique et de l'activité du noyau sous-thalamique dans l'occurrence du trouble est suggérée, et les perspectives thérapeutiques discutées / Response inhibition plays a major role in cognitive control. Understanding these mechanisms is essential because their dysfunctions may cause symptoms in many psychiatric and neurological diseases. The relationship between brain activity and behavior are particularly difficult to understand because the function of interest is specifically intended to prevent any observable behavior… In the first part, we propose a review of issues highlighting the need for a new theoretical model and adapted psychophysical methods. We also provide systematic analysis of studies using electroencephalography, widely preferred method for probing the dynamics of inhibitory mechanisms. Convergently, the review calls for revisiting both acquisition methods and processing methods of EEG signal used in conventional studies. In the second part, we implement these proposals by combining advanced treatment methods of EEG signal (blind source separation, analysis test by test, spectral analysis in the sources, location) and comparing these results with the fMRI data. We reveal the involvement of automatic and nonselective inhibitory mechanisms, when the context is uncertain. A large medial frontoparietal network would ensure the implementation. The involvement of an automatic behavior (when the environment becomes predictable) would require a top-down control that deactivates in advance the excitability of the self-inhibitory circuitry of the SMC. In the third and fourth sections, we show the key role of this function in other cognitive processes and illustrate the clinical consequences of its dysfunction. We show in particular that the difficulty in initiating an action (akinesia) would, in Parkinson’s disease, a direct consequence of this dysfunction. The involvement of the noradrenergic system and the activity of the subthalamic nucleus in the occurrence of the disorder are suggested, and therapeutic perspectives discussed

Par sa connectivité directe avec le cortex, le noyau subthalamique (NST) représente une des structures d'entrée du système des ganglions de la base, et se trouve impliqué dans différents aspects du comportement (contrôle moteur, cognitif et limbique). Néanmoins, les corrélats électrophysiologiques de ces processus restent débattus. Les études effectuées dans le cadre de cette thèse visent à éclaircir le rôle possible du NST dans trois fonctions exécutives, à savoir l'inhibition réactive (suppression d'un mouvement programmé), l'inhibition proactive (préparation à inhiber son mouvement) et l'attention soutenue. Pour ce faire, les activités extracellulaires et/ou en potentiels de champs locaux du NST ont été enregistrées chez 28 patients parkinsoniens pendant qu'ils effectuaient des taches cognitives, visant à dissocier les corrélats de ces différentes fonctions exécutives. Dans une première étude, les activités en potentiel de champs locaux du NST lors de l'inhibition réactive et proactive ont été étudiées à l'aide d'un paradigme modifié du « stop signal ». L'inhibition réactive se caractérise par une augmentation rapide de synchronisation relative de l'activité du NST dans la bande de fréquence β (13-35 Hz), tandis que l'inhibition proactive se caractérise par la maintenance tonique d'un niveau élevé d'activité β qui prédit les performances des patients lors de l'inhibition réactive. Dans la seconde étude, nous avons montré qu'une population neuronale (n=7 neurones) augmente rapidement sa fréquence de décharge lors de l'inhibition réactive. Enfin, dans la troisième étude, nous avons utilisé un paradigme permettant de moduler le niveau attentionnel requis pour réaliser un comportement simple. Nos résultats indiquent qu'une baisse d'activité β est observée uniquement lorsque le sujet maintient une attention soutenue pour encoder, retrouver en mémoire une information afin de produire une réponse. L'ensemble de ces résultats nous ont permis d'apporter des preuves électrophysiologiques de l'implication du NST dans ces différentes fonctions et de clarifier la dynamique temporelle des activités neuronales supportant ces processus. Ils suggèrent ainsi l'hypothèse d'une implémentation de différents aspects du contrôle exécutif dans le NST via des mécanismes communs et interactifs dont la dynamique temporelle permettrait la modulation fine du comportement. / The subthalamic nucleus (STN) is an input structure of the basal ganglia implicated in many behavioral processes (motor, cognitive and limbic control). However the electrophysiological correlates of these processes remain unclear. This thesis aims to clarify the role of the STN during 3 executive functions: reactive inhibition (suppression of a prepotent move), proactive inhibition (preparation to inhibit a move) and sustained attention. To this end, extracellular and local field potential activities were recorded in 28 patients with Parkinson's disease while they performed cognitive tasks, aiming to dissociate the neural correlates of these executive functions In a first study, local field potentials β (13-35 Hz) activity was recorded in the STN during reactive and proactive inhibition. Reactive Inhibition was related to a relative increase of β activity, while proactive inhibition was related to maintenance of a tonic level of β activity predictive of reactive inhibitory performances. In a second study, we showed that reactive inhibition is related to a phasic increase of firing rate in a neuronal subpopulation (n=7 neurons). In a third study, we recorded Local field potentials in the STN while patients performed a sustained attention-demanding task (combining a visual search and a delayed match-to-sample paradigm) and found a systematic suppression of 15-35 Hz activity during each repetition of the task directly related to the amount of attention allocated by the participants. Altogether, these results present electrophysiological evidences of the implication of the STN in these functions and clarify the temporal dynamics of neuronal activities supporting these processes. These results may suggest an implementation of various executive functions in the STN via common and interactive mechanisms which temporal dynamics would mediate behavioral control.

Uma série de estudos na literatura vêm demonstrando a necessidade de intervenções voltadas para adultos portadores do transtorno do espectro do autismo, cuja situação de exclusão social somadas às necessidades crescentes do mundo atual de flexibilidade e engajamento podem levar a problemas emocionais, como ansiedade e depressão. O foco deste estudo foi baseado em funções executivas (FEs) real-world, isto é, focado no funcionamento diário bemsucedido e adaptativo. Este estudo pretendeu: 1) apresentar uma revisão bibliográfica para melhor compreensão do desenvolvimento das FEs em indivíduos com TEA; 2) apresentar uma intervenção neurodesenvolvimental global, o método Ramain; 3) apresentar como ilustração um estudo longitudinal de caso de 4 anos e 6 meses de intervenção (1 sessão semanal de 2 hr e 30 min) e de follow-up de 2 e 5 anos, relativo a um jovem adulto portador de TEA atendido por meio desse método. O método buscou ativar as FEs e mobilizar simultaneamente as funções cognitivas, motoras, emocionais e sociais. Concluiu-se através de observação de duas escalas e de marcadores de ganho de autonomia tanto em espaço terapêutico, como na vida cotidiana (por meio dos relatos de pais e profissionais), que houve aprimoramento das FEs e uma evolução significativa na adaptabilidade, no desenvolvimento das habilidades psicossociais, da autonomia e na qualidade de vida desse adulto, o que abre a possibilidade do uso de intervenções globais em casos de indivíduos com TEA / Several studies in literature have indicated the need for interventions targeting adults with autism spectrum disorder, whose social exclusion, coupled with today\'s increasing needs for flexibility and engagement, may lead to emotional problems such as anxiety and depression. The focus of this study was based on real-world (EFs) executive functions, that is, focused on successful and adaptive daily functioning. The purpose of this study was to: 1) present a bibliographical review for better comprehension of the development of EFs in individuals with ASD; 2) present a global neurodevelopmental intervention, i.e., the Ramain method; 3) present, as an illustration, a longitudinal case study of 4 years and 6 months of intervention (1 weekly session of 2 hr and 30 min) and 2- and 5-year follow-up of a young adult ASD patient, through this method. The method sought to activate EFs and simultaneously mobilize cognitive, motor, emotional and social functions. It was concluded through the observation of two scales and markers of autonomy gain both in therapeutic space and in daily life (through reports of parents and professionals) that there was an improvement of EFs and significant evolution in adaptability, in the development of psychosocial skills, autonomy and quality of life of this adult, which opens the possibility of using global interventions in cases of individuals with ASD

<p>The central theme of the present thesis revolves around the exploration of similarities and differences in brain activity patterns invoked by the component processes underlying mnemonic, executive and attentional functions. The primary aim was to identify and functionally characterize commonly recruited brain regions in terms of shared component processes, which has been a largely neglected area of research in cognitive neuroscience. The vast majority of functional brain imaging investigations of cognition has focused on delineating differences between cognitive functions or processes, with the purpose of isolating the unique functional neuroanatomy that underlies specific cognitive domains. By contrast, the present thesis builds on the results from three imaging studies that focused primarily on detecting commonalities in functional brain activity across different forms of memory processes. In study I, the imaging data from two positron emission tomography (PET) experiments were re-analyzed to identify common activation patterns associated with nine different memory tasks incorporated across the experiments, three each separately indexing working memory, episodic memory, and semantic memory. A generic prefrontal cortex (PFC) network involving discrete subregions of the left hemisphere located in ventrolateral (BA 45/47), dorsolateral (BA 9/44/46), and frontopolar (BA 10) sectors of PFC, as well as a midline portion of the frontal lobes, encompassing the dorsal part of the anterior cingulate cortex (ACC) (BA 24/32), was conjointly recruited across all tasks. In study II, we used a novel mixed blocked/event-related functional magnetic resonance imaging (fMRI) design, which enables separation of brain responses associated with different temporal dynamics to further investigate commonalities of neural activation across working memory, episodic memory, semantic memory, and attention/vigilance. A similar set of common PFC regions, as that discovered in Study I, was found to elicit overlapping brain activity across all memory tasks, with a subset of regions also activated in the attention/vigilance task. Furthermore, the task-induced brain activity was dissociated in terms of the temporal profiles of the evoked neural responses. A common pattern of sustained activity seen across all memory tasks and the attention task involved bilateral (predominantly right-lateralized) ventrolateral PFC (BA 45/47), and the dorsal ACC (BA 24/32), which was assumed to reflect general processes of attention/vigilance. A pattern of sustained activity elicited in all memory tasks, in the absence of attention-related activity, involved the right frontopolar cortex (BA 10), which was assumed to reflect control processes underlying task set maintenance. In addition, common transient activation evoked in the memory tasks relative to the attention task was found in the dorsolateral (BA 9/44) and ventrolateral (BA 47) PFC, the superior parietal cortex (BA 7), and cerebellum. In study III, a mixed fMRI design was used to assess the degree of common brain activity associated with increased executive demand, which was independently manipulated within episodic and working memory. Unitary control modulations involved a shared tonic executive component subserved by fronto-striatal-cerebellar circuitry, assumed to govern top-down context processing throughout task periods, and a stimulus-synchronous phasic component mediated by the intraparietal sulcus (BA 7), assumed to support dynamic shifting of the ‘focus of attention’ among internal representations. Collectively, the theoretical implications of shared neural mechanisms are discussed, with a special focus on human memory and its multifaceted relationships with attention and executive control functions. Finally, the presented imaging data are used to outline a tentative hierarchical neurocognitive model that attempts to give an account of how different unitary component processes might work together during cognitive task performance.</p>

Les hormones thyroïdiennes sont importantes à la fois pour le développement, la maturation et le fonctionnement du système nerveux central tout au long de la vie. Alors que l’association entre l’absence d’hormones thyroïdiennes dans l’hypothyroïdie congénitale et le retard mental profond est bien documentée, l’hypothyroïdie acquise à l’âge adulte peut se manifester par une variété de symptômes tant somatiques, que neuropsychologiques ou psychiatriques comme des troubles de l’attention, troubles de la concentration, troubles de mémoire, un ralentissement psychomoteur mais aussi une humeur dépressive, de l’anxiété et même parfois un délire de persécution. De plus, les processus physiopathologiques reliant l’activité thyroïdienne à ces symptômes restent peu clairs dans l’hypothyroïdie acquise à l’âge adulte. L’objectif de cette thèse est d’examiner les relations entre état hypothyroïdien et dépression. En utilisant des échelles psychométriques, dix patients thyroïdectomisés pour carcinome thyroïdien ont été évalués pour la dépression, l’anxiété et le ralentissement psychomoteur ; ils ont été examinés à la fois en eu- et hypothyroïdie après retrait des hormones thyroïdiennes. Une tomographie par émission de positrons a été utilisée, avec de l’eau marquée à l’oxygène-15 et du fluorodéoxyglucose marqué au fluor-18 comme traceurs, de manière à corréler le débit sanguin cérébral régional (rDSC) et le métabolisme cérébral au glucose (rMGC) avec l’état mental des patients. Deux techniques différentes d’analyse d’images ont été appliquées (régions d’intérêt et cartes statistiques paramétriques). En hypothyroïdie, il y avait une diminution généralisée du rDSC (23.4%, p<0.001) et du rMGC (12.1%, p<0.001) sans diminution locale spécifique. Les patients étaient aussi significativement plus déprimés (p<0.001), plus anxieux (p<0.001) et plus ralentis sur le plan psychomoteur (p<0.005) en hypothyroïdie qu’à l’état euthyroïdien. Ces résultats indiquent que l’activité cérébrale est globalement réduite en hypothyroïdie sévère de courte durée sans observation des modifications régionales habituellement décrites dans la dépression majeure. Nous avons ensuite conduit une étude cognitive qui a examiné les fonctions attentionnelles, mnésiques et exécutives de même que l’intensité des symptômes anxieux et dépressifs dans l’état hypothyroïdien et le trouble dépressif majeur et le lien possible entre ces symptômes et les perturbations cognitives. Cette étude a confirmé l’existence d’un ralentissement psychomoteur associé à des perturbations attentionnelles et exécutives mais non mnésiques dans la dépression majeure, de même que dans l’hypothyroïdie. Cependant, alors que les patients déprimés présentaient un biais conscient pour du matériel à valence émotionnelle négative, ce biais n’a pas été observé chez les patients hypothyroïdiens. Alors que l’état hypothyroïdien s’accompagnait de symptômes anxieux et dépressifs, il semble que ces derniers soient trop discrets pour qu’un biais attentionnel puisse être observé avec du matériel à valence émotionnelle négative. En conclusion, les perturbations cognitives observées en hypothyroïdie semblent être directement reliées à cette condition métabolique hypothyroïdienne plutôt que la conséquence des symptômes dépressifs associés à cette condition. / The thyroid hormone is important both for the functional development and maturation of the central nervous system and for its proper functioning throughout life. Whereas the association between the absence of thyroid hormone in congenital hypothyroidism and profound mental retardation is well documented, adult onset hypothyroidism may have a variety of somatic, neuropsychological and psychiatric symptoms such as inattentiveness, inability to concentrate, deficits in memory, psychomotor slowing but also depressive mood state, anxiety, and sometimes persecutive delusions. In addition, the pathophysiological process relating thyroid activity to these symptoms remain unclear in adult onset hypothyroidism. The objective of this thesis is to examine the relationships between hypothyroidism and depression. Using psychometric scales, ten patients that had undergone total thyroidectomy for thyroid carcinoma were evaluated for depression, anxiety and psychomotor slowing; they were examined both when euthyroid and hypothyroid after thyroid hormone withdrawal. Positron emission tomography was used, with oxygen-15-labeled water and fluorine-18 FDG as the tracers, to correlate the regional cerebral blood flow (rCBF) and cerebral glucose metabolism (rCMRGlc) with the mental state in patients. Two different image analysis techniques (regions of interest and statistical parametric maps) were applied. In hypothyroidism, there was a generalized decrease in rCBF (23.4%, p<0.001) and in rCMRGlc (12.1%, p<0.001) and there were no specific local defects. Patients were also significantly more depressed (p<0.001), anxious (p<0.001) and psychomotor slowed (p<0.005) in hypo- than in euthyroid status. These results indicate that the brain activity was globally reduced in severe hypothyroidism of short duration without the regional modifications usually observed in primary depression. We conducted then a cognitive study which examined attentional, mnemonic and executive functions as well as the intensity of anxiety and depressive symptoms in hypothyroidism and major depression and the possible link between these symptoms and cognitive disturbances. This study confirmed the existence of psychomotor slowing associated with attentional and executive disturbance but without mnemonic disturbances in major depression as well as in hypothyroidism. However, while depressed subjects manifested a conscious bias with material of negative emotional valence, no such bias was found in the hypothyroid subjects. While the hypothyroid state is accompanied by anxiety/depressive symptoms, it seems that the latter are too discrete for an attentional bias to be observed with material with a negative emotional valence. In conclusion, the cognitive disturbances observed in hypothyroidism seem to be directly related to the metabolic condition of hypothyroidism rather than the consequence of the depressive symptoms associated with this condition.