Le trouble obsessionnel-compulsif (TOC) est un trouble anxieux fréquent et invalidant. Pour un grand nombre de patients, il existe une résistance aux thérapeutiques actuellement disponibles, soulignant toute l'importance de mieux préciser la physiopathologie du TOC. Le principal objectif de cette thèse est d’étudier les altérations anatomiques et fonctionnelles des voies thalamo-corticales intéressant le cortex orbitofrontal (COF) et le cortex cingulaire antérieur (CCA) dans le TOC. Pour cela, nous avons utilisé plusieurs outils complémentaires permettant d’appréhender cette problématique sous différents angles méthodologiques.Concernant les altérations anatomiques associées au TOC, nous avons rapporté les données de méta-analyses des études de neuro-imagerie volumétrique et morphométrique ainsi que les résultats d'une étude originale d'imagerie volumétrique. Une diminution du volume orbitofrontal, une augmentation du volume thalamique et une relation entre ces modifications de volumes ont été observées chez les patients avec TOC comparativement aux témoins. Les modifications de densité de matière grise concernaient le COF et le putamen dans le sens d'une augmentation et les cortex pariétal et préfrontal dorsolatéral dans le sens d'une diminution dans le TOC.Concernant les altérations fonctionnelles associées au TOC, nous avons détaillé un travail de méta-analyse des études d'imagerie fonctionnelle, un travail expérimental chez le primate basé sur des manipulations pharmacologiques intra-cérébrales, puis un travail expérimental chez l'homme reposant sur le développement d'une tâche comportementale originale couplée à l'imagerie fonctionnelle. Dans notre méta-analyse, nous avons décrit la participation fonctionnelle de régions comme le COF, le thalamus et le striatum lorsque des symptômes obsessionnels et compulsifs étaient provoqués chez des patients. Chez le primate subhumain, nous avons montré qu'une hyperactivation du noyau ventral-antérieur, par levée de l'inhibition GABAergique, entraînait l'apparition de comportements pseudo-compulsifs. Ensuite, à l'aide d'une tâche originale qui mettait les sujets en situation de vérifier, nous avons mis en évidence que les dysfonctions orbitofrontales associées au doute lors de la prise de décision n'étaient pas modulées ni par les informations contextuelles (signaux d'erreur), ni par la réponse comportementale chez les patients avec TOC comparativement à des sujets témoins.Enfin, la superposition des cartes morphométriques et fonctionnelles a trouvé une relation entre les altérations anatomiques et fonctionnelles au sein du COF. Nos résultats soulignent toute l'importance des voies thalamo-orbitofrontales dans la physiopathologie du TOC. / Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Available treatments are effective for most patients but impairing residual symptoms and treatment resistance are common in OCD patients. Therefore, a better understanding of OCD pathophysiology is essential for further improvement of therapeutic strategies. The main goal of my thesis was to assess the anatomical and funtional thalamocortical alterations associated with OCD. Concerning the anatomical thalamocortical alterations associated with OCD, we conducted two meta-analyses of anatomical neuroimaging studies and an original volumetric neuroimaging study. We reported a smaller thalamic volume and a greater orbitofrontal volume, but also an inverse relationship between the volume changes in OCD patients compared with healthy subjects. Furthermore, we showed that gray matter density within the orbitofrontal cortex and the putamen were enhanced in OCD. Concerning the functional thalamocortical alterations associated with OCD, we reported data coming from a meta-analysis of functional neuroimaging studies, an experimental study in subhuman primates using local brain pharmacological manipulations and an event-related neuroimaging study in OCD patients. In our meta-analysis, we showed that the orbitofrontal cortex, the thalamus and the striatum were involved in the mediation of OCD symptoms. In subhuman primates, the pharmacologically induced overactivity within the ventralanterior thalamic nucleus leaded to the emergence of compulsive-like behaviors. Then, in our neuroimaging study, we found that doubt-related orbitofrontal dysfunctions were not modulated by neither error signals nor compulsive-like behaviors in OCD patients, compared with healthy subjects. Finally, we described by using meta-analytic data that anatomical and functional brain alterations overlap with the lateral orbitofrontal cortex in OCD. In conclusion, our results suggest that the thalamo-orbitofrontal network may play a primary role in the genesis and mediation of OCD symptoms.

Modelos experimentais do transtorno obsessivo compulsivo (TOC) com humanos mostram que uma forma de evocar comportamentos de checagem é apresentar instruções que especificam consequências aversivas para o comportamento inefetivo na execução de tarefas. Atualmente há na área somente um estudo experimental com delineamento de sujeito único. Os presentes dois experimentos com 16 participantes verbalmente habilidosos tiveram o objetivo de testar se instruções com especificação de consequência aversiva ou apetitiva poderiam ter o efeito de produzir respostas de checagem. Em um restaurante experimental, as instruções foram apresentadas durante uma tarefa de separação de sementes misturadas. No Experimento 1, cinco de oito participantes apresentaram maiores porcentagens de checagens sob especificação de consequência aversiva. No Experimento 2, sete de oito participantes apresentaram maiores porcentagens sob especificação de consequência apetitiva. Concluiu-se que determinadas instruções alteraram a função discriminativa e/ou motivadora dos estímulos envolvidos na tarefa experimental. Sugere-se que o presente delineamento pode permitir a formulação de análises funcionais do fenômeno comportamental normalmente envolvido em alguns casos de TOC / Experimental models of obsessive compulsive disorder (OCD) with humans show that a way to evoke checking behaviors is to provide instructions that specify aversive consequences for behavior ineffective in performing tasks. Currently there is only one experimental study with a single subject design in this area. The present study presents two experiments with 16 verbally skilled participants tested whether instructions specifying the appetitive or aversive consequence could have the effect of producing checking behaviors. In an experimental restaurant, the instructions were presented during a task of separation of mixed seeds. In Experiment 1, five of eight participants showed higher percentages of checks under specification of aversive consequence. In Experiment 2, seven of eight participants had higher percentages under specification of appetitive consequence. It was concluded that certain instructions alter the discriminative and motivate function of the stimuli involved in experimental task. It is suggested that this design may allow the formulation of functional analysis of behavioral phenomenon normally involved in some cases of OCD

Modelos experimentais do transtorno obsessivo compulsivo (TOC) com humanos mostram que uma forma de evocar comportamentos de checagem é apresentar instruções que especificam consequências aversivas para o comportamento inefetivo na execução de tarefas. Atualmente há na área somente um estudo experimental com delineamento de sujeito único. Os presentes dois experimentos com 16 participantes verbalmente habilidosos tiveram o objetivo de testar se instruções com especificação de consequência aversiva ou apetitiva poderiam ter o efeito de produzir respostas de checagem. Em um restaurante experimental, as instruções foram apresentadas durante uma tarefa de separação de sementes misturadas. No Experimento 1, cinco de oito participantes apresentaram maiores porcentagens de checagens sob especificação de consequência aversiva. No Experimento 2, sete de oito participantes apresentaram maiores porcentagens sob especificação de consequência apetitiva. Concluiu-se que determinadas instruções alteraram a função discriminativa e/ou motivadora dos estímulos envolvidos na tarefa experimental. Sugere-se que o presente delineamento pode permitir a formulação de análises funcionais do fenômeno comportamental normalmente envolvido em alguns casos de TOC / Experimental models of obsessive compulsive disorder (OCD) with humans show that a way to evoke checking behaviors is to provide instructions that specify aversive consequences for behavior ineffective in performing tasks. Currently there is only one experimental study with a single subject design in this area. The present study presents two experiments with 16 verbally skilled participants tested whether instructions specifying the appetitive or aversive consequence could have the effect of producing checking behaviors. In an experimental restaurant, the instructions were presented during a task of separation of mixed seeds. In Experiment 1, five of eight participants showed higher percentages of checks under specification of aversive consequence. In Experiment 2, seven of eight participants had higher percentages under specification of appetitive consequence. It was concluded that certain instructions alter the discriminative and motivate function of the stimuli involved in experimental task. It is suggested that this design may allow the formulation of functional analysis of behavioral phenomenon normally involved in some cases of OCD