Aglomerados de galáxias são as maiores estruturas no Universo. Sua distribuição mapeia os halos de matéria escura formados nos potenciais profundos do campo de matéria escura. Consequentemente, a abundância de aglomerados é altamente sensível a expansão do Universo, assim como ao crescimento das perturbações de matéria escura, constituindo uma poderosa ferramenta para fins cosmológicos. Na era atual de grandes levantamentos observacionais que produzem uma quantidade gigantesca de dados, as propriedades estatísticas dos objetos observados (galáxias, aglomerados, supernovas, quasares, etc) podem ser usadas para extrair informações cosmológicas. Para isso, é necessária o estudo da formação de halos de matéria escura, da detecção dos halos e aglomerados, das ferramentas estatísticas usadas para o vínculos de parâmetros, e finalmente, dos efeitos da detecções ópticas. No contexto da formulação da predição teórica da contagem de halos, foi analisada a influência de cada parâmetro cosmológico na abundância dos halos, a importância do uso da covariância dos halos, e a eficácia da utilização dos halos para vincular cosmologia. Também foi analisado em detalhes os intervalos de redshift e o uso de conhecimento prévio dos parâmetros ({\\it priors}). A predição teórica foi testada um uma simulação de matéria escura, onde a cosmologia era conhecida e os halos de matéria escura já haviam sido detectados. Nessa análise, foi atestado que é possível obter bons vínculos cosmológicos para alguns parâmetros (Omega_m,w,sigma_8,n_s), enquanto outros parâmetros (h,Omega_b) necessitavam de conhecimento prévio de outros testes cosmológicos. Na seção dos métodos estatísticos, foram discutidos os conceitos de {\\it likelihood}, {\\it priors} e {\\it posterior distribution}. O formalismo da Matriz de Fisher, bem como sua aplicação em aglomerados de galáxias, foi apresentado e usado para a realização de predições dos vínculos em levantamentos atuais e futuros. Para a análise de dados, foram apresentados métodos de Cadeias de Markov de Monte Carlo (MCMC), que diferentemente da Matriz de Fisher não assumem Gaussianidade entre os parâmetros vinculados, porém possuem um custo computacional muito mais alto. Os efeitos observacionais também foram estudados em detalhes. Usando uma abordagem com a Matriz de Fisher, os efeitos de completeza e pureza foram extensivamente explorados. Como resultado, foi determinado em quais casos é vantajoso incluir uma modelagem adicional para que o limite mínimo de massa possa ser diminuído. Um dos principais resultados foi o fato que a inclusão dos efeitos de completeza e pureza na modelagem não degradam os vínculos de energia escura, se alguns outros efeitos já estão sendo incluídos. Também foi verificados que o uso de priors nos parâmetros não cosmológicos só afetam os vínculos de energia escura se forem melhores que 1\\%. O cluster finder(código para detecção de aglomerados) WaZp foi usado na simulação, produzindo um catálogo de aglomerados. Comparando-se esse catálogo com os halos de matéria escura da simulação, foi possível investigar e medir os efeitos observacionais. A partir dessas medidas, pôde-se incluir correções para a predição da abundância de aglomerados, que resultou em boa concordância com os aglomerados detectados. Os resultados a as ferramentas desenvolvidos ao longo desta tese podem fornecer um a estrutura para a análise de aglomerados com fins cosmológicos. Durante esse trabalho, diversos códigos foram desenvolvidos, dentre eles, estão um código eficiente para computar a predição teórica da abundância e covariância de halos de matéria escura, um código para estimar a abundância e covariância dos aglomerados de galáxias incluindo os efeitos observacionais, e um código para comparar diferentes catálogos de halos e aglomerados. Esse último foi integrado ao portal científico do Laboratório Interinstitucional de e-Astronomia (LIneA) e está sendo usado para avaliar a qualidade de catálogos de aglomerados produzidos pela colaboração do Dark Energy Survey (DES), assim como também será usado em levantamentos futuros. / Abstract Galaxy clusters are the largest bound structures of the Universe. Their distribution maps the dark matter halos formed in the deep potential wells of the dark matter field. As a result, the abundance of galaxy clusters is highly sensitive to the expansion of the universe as well as the growth of dark matter perturbations, representing a powerful tool for cosmological purposes. In the current era of large scale surveys with enormous volumes of data, the statistical quantities from the objects surveyed (galaxies, clusters, supernovae, quasars, etc) can be used to extract cosmological information. The main goal of this thesis is to explore the potential use of galaxy clusters for constraining cosmology. To that end, we study the halo formation theory, the detection of halos and clusters, the statistical tools required to quarry cosmological information from detected clusters and finally the effects of optical detection. In the composition of the theoretical prediction for the halo number counts, we analyze how each cosmological parameter of interest affects the halo abundance, the importance of the use of the halo covariance, and the effectiveness of halos on cosmological constraints. The redshift range and the use of prior knowledge of parameters are also investigated in detail. The theoretical prediction is tested on a dark matter simulation, where the cosmology is known and a dark matter halo catalog is available. In the analysis of the simulation we find that it is possible to obtain good constraints for some parameters such as (Omega_m,w,sigma_8,n_s) while other parameters (h,Omega_b) require external priors from different cosmological probes. In the statistical methods, we discuss the concept of likelihood, priors and the posterior distribution. The Fisher Matrix formalism and its application on galaxy clusters is presented, and used for making forecasts of ongoing and future surveys. For the real analysis of data we introduce Monte Carlo Markov Chain (MCMC) methods, which do not assume Gaussianity of the parameters distribution, but have a much higher computational cost relative to the Fisher Matrix. The observational effects are studied in detail. Using the Fisher Matrix approach, we carefully explore the effects of completeness and purity. We find in which cases it is worth to include extra parameters in order to lower the mass threshold. An interesting finding is the fact that including completeness and purity parameters along with cosmological parameters does not degrade dark energy constraints if other observational effects are already being considered. The use of priors on nuisance parameters does not seem to affect the dark energy constraints, unless these priors are better than 1\\%.The WaZp cluster finder was run on a cosmological simulation, producing a cluster catalog. Comparing the detected galaxy clusters to the dark matter halos, the observational effects were investigated and measured. Using these measurements, we were able to include corrections for the prediction of cluster counts, resulting in a good agreement with the detected cluster abundance. The results and tools developed in this thesis can provide a framework for the analysis of galaxy clusters for cosmological purposes. Several codes were created and tested along this work, among them are an efficient code to compute theoretical predictions of halo abundance and covariance, a code to estimate the abundance and covariance of galaxy clusters including multiple observational effects and a pipeline to match and compare halo/cluster catalogs. This pipeline has been integrated to the Science Portal of the Laboratório Interinstitucional de e-Astronomia (LIneA) and is being used to automatically assess the quality of cluster catalogs produced by the Dark Energy Survey (DES) collaboration and will be used in other future surveys.

Objetivos: Malformação de Chiari do tipo I (MC-I) é a principal doença malformativa congênita da junção craniovertebral, manifestando-se com ampla variedade de sinais e sintomas neurológicos. A melhor técnica cirúrgica a ser empregada no tratamento dos pacientes com malformação de Chiari do tipo I é ainda controversa. A descompressão das estruturas da fossa craniana posterior com plástica de ampliação dural é considerada procedimento padrão. Embora efetiva e de baixa morbidade, a craniectomia occipital isolada, sem abertura e ampliação dural, implica maior taxa de recidiva dos sintomas. Métodos que selecionam os pacientes quanto a necessidade da duroplastia não foram estabelecidos. O presente trabalho avalia a eficácia da mensuração intraoperatória da velocidade do fluxo do líquido cefalorraquidiano através da ultrassonografia (USG) na seleção da técnica cirúrgica a ser utilizada. Métodos: Foram analisados de forma prospectiva 49 pacientes submetidos à cirurgia para MC-I. A indicação de craniectomia da fossa posterior associada ou não à plástica de ampliação da dura-máter baseou-se na velocidade do fluxo do líquido cefalorraquidiano, mensurada pela ultrassonografia intraoperatória. Dor cervical, cefaleia e qualidade de vida foram avaliadas antes e após o tratamento cirúrgico. Resultados: Dos 49 pacientes incluídos, 36 pacientes (73%) apresentavam fluxo do líquido cefalorraquidiano superior a 3 cm/s e não foram submetidos a duroplastia ampliadora. Nos 13 (27%) pacientes com fluxo inicial inferior a 3 cm/s, indicou-se craniectomia occipital com duroplastia de ampliação. Não houve diferença significativa entre os dois grupos com relação aos parâmetros estudados. Conclusão: A ultrassonografia intraoperatória com avaliação da dinâmica e velocidade do fluxo do líquido cefalorraquidiano da junção craniovertebral auxilia a indicação de duroplastia durante descompressão da fossa craniana posterior em pacientes adultos com MC-I / Objectives: Chiari malformation Type I (CM-I) is the main congenital malformation disease of the craniovertebral junction, and may be responsible for a variety of neurological symptoms. The ideal surgical technique used to treat patients with CM-I is still controversial. Invasive procedures that enters CSF space and are associated with dural repair, are considered the gold standard. Although effective and less morbidity, isolated bone decompression without dural opening, implies greater recurrence of symptoms. Objective parameters to select patients, who need or not to have a duroplasty performed, have not been established. Our study evaluates the efficacy of intra-operative CSF flow measurement through the use of ultrasonography (USG) as a determining parameter in the selection of these patients. Methods: We analyzed prospectively 49 posterior fossa surgeries for patients with CM-I. Patients underwent decompressive surgery with or without opening of the dura mater after conducting USG intra-operatively with measured flow rate, being adopted 3cm/s flow rate as a determining value. The quality of life before and after surgery and the improvement of neck pain and headache were the parameters evaluated. Results: Of the 49 patients enrolled, 36 patients (73%) had adequate CSF flow above 3 cm / s and have not undergone duroplasty. In 13 (27%) patients with initial flow < 3 cm / s an opening in dura mater was performed together with duroplasty. There was no significant difference between the two groups regarding the parameters studied. Conclusion: Intraoperative ultrasound with measurement of CSF flow, having a flow of 3 cm / s as cut-off, allows the proper selection of patients with CM-I that can have a less invasive surgery with bone decompression without duroplasty

Aglomerados de galáxias são as maiores estruturas no Universo. Sua distribuição mapeia os halos de matéria escura formados nos potenciais profundos do campo de matéria escura. Consequentemente, a abundância de aglomerados é altamente sensível a expansão do Universo, assim como ao crescimento das perturbações de matéria escura, constituindo uma poderosa ferramenta para fins cosmológicos. Na era atual de grandes levantamentos observacionais que produzem uma quantidade gigantesca de dados, as propriedades estatísticas dos objetos observados (galáxias, aglomerados, supernovas, quasares, etc) podem ser usadas para extrair informações cosmológicas. Para isso, é necessária o estudo da formação de halos de matéria escura, da detecção dos halos e aglomerados, das ferramentas estatísticas usadas para o vínculos de parâmetros, e finalmente, dos efeitos da detecções ópticas. No contexto da formulação da predição teórica da contagem de halos, foi analisada a influência de cada parâmetro cosmológico na abundância dos halos, a importância do uso da covariância dos halos, e a eficácia da utilização dos halos para vincular cosmologia. Também foi analisado em detalhes os intervalos de redshift e o uso de conhecimento prévio dos parâmetros ({\\it priors}). A predição teórica foi testada um uma simulação de matéria escura, onde a cosmologia era conhecida e os halos de matéria escura já haviam sido detectados. Nessa análise, foi atestado que é possível obter bons vínculos cosmológicos para alguns parâmetros (Omega_m,w,sigma_8,n_s), enquanto outros parâmetros (h,Omega_b) necessitavam de conhecimento prévio de outros testes cosmológicos. Na seção dos métodos estatísticos, foram discutidos os conceitos de {\\it likelihood}, {\\it priors} e {\\it posterior distribution}. O formalismo da Matriz de Fisher, bem como sua aplicação em aglomerados de galáxias, foi apresentado e usado para a realização de predições dos vínculos em levantamentos atuais e futuros. Para a análise de dados, foram apresentados métodos de Cadeias de Markov de Monte Carlo (MCMC), que diferentemente da Matriz de Fisher não assumem Gaussianidade entre os parâmetros vinculados, porém possuem um custo computacional muito mais alto. Os efeitos observacionais também foram estudados em detalhes. Usando uma abordagem com a Matriz de Fisher, os efeitos de completeza e pureza foram extensivamente explorados. Como resultado, foi determinado em quais casos é vantajoso incluir uma modelagem adicional para que o limite mínimo de massa possa ser diminuído. Um dos principais resultados foi o fato que a inclusão dos efeitos de completeza e pureza na modelagem não degradam os vínculos de energia escura, se alguns outros efeitos já estão sendo incluídos. Também foi verificados que o uso de priors nos parâmetros não cosmológicos só afetam os vínculos de energia escura se forem melhores que 1\\%. O cluster finder(código para detecção de aglomerados) WaZp foi usado na simulação, produzindo um catálogo de aglomerados. Comparando-se esse catálogo com os halos de matéria escura da simulação, foi possível investigar e medir os efeitos observacionais. A partir dessas medidas, pôde-se incluir correções para a predição da abundância de aglomerados, que resultou em boa concordância com os aglomerados detectados. Os resultados a as ferramentas desenvolvidos ao longo desta tese podem fornecer um a estrutura para a análise de aglomerados com fins cosmológicos. Durante esse trabalho, diversos códigos foram desenvolvidos, dentre eles, estão um código eficiente para computar a predição teórica da abundância e covariância de halos de matéria escura, um código para estimar a abundância e covariância dos aglomerados de galáxias incluindo os efeitos observacionais, e um código para comparar diferentes catálogos de halos e aglomerados. Esse último foi integrado ao portal científico do Laboratório Interinstitucional de e-Astronomia (LIneA) e está sendo usado para avaliar a qualidade de catálogos de aglomerados produzidos pela colaboração do Dark Energy Survey (DES), assim como também será usado em levantamentos futuros. / Abstract Galaxy clusters are the largest bound structures of the Universe. Their distribution maps the dark matter halos formed in the deep potential wells of the dark matter field. As a result, the abundance of galaxy clusters is highly sensitive to the expansion of the universe as well as the growth of dark matter perturbations, representing a powerful tool for cosmological purposes. In the current era of large scale surveys with enormous volumes of data, the statistical quantities from the objects surveyed (galaxies, clusters, supernovae, quasars, etc) can be used to extract cosmological information. The main goal of this thesis is to explore the potential use of galaxy clusters for constraining cosmology. To that end, we study the halo formation theory, the detection of halos and clusters, the statistical tools required to quarry cosmological information from detected clusters and finally the effects of optical detection. In the composition of the theoretical prediction for the halo number counts, we analyze how each cosmological parameter of interest affects the halo abundance, the importance of the use of the halo covariance, and the effectiveness of halos on cosmological constraints. The redshift range and the use of prior knowledge of parameters are also investigated in detail. The theoretical prediction is tested on a dark matter simulation, where the cosmology is known and a dark matter halo catalog is available. In the analysis of the simulation we find that it is possible to obtain good constraints for some parameters such as (Omega_m,w,sigma_8,n_s) while other parameters (h,Omega_b) require external priors from different cosmological probes. In the statistical methods, we discuss the concept of likelihood, priors and the posterior distribution. The Fisher Matrix formalism and its application on galaxy clusters is presented, and used for making forecasts of ongoing and future surveys. For the real analysis of data we introduce Monte Carlo Markov Chain (MCMC) methods, which do not assume Gaussianity of the parameters distribution, but have a much higher computational cost relative to the Fisher Matrix. The observational effects are studied in detail. Using the Fisher Matrix approach, we carefully explore the effects of completeness and purity. We find in which cases it is worth to include extra parameters in order to lower the mass threshold. An interesting finding is the fact that including completeness and purity parameters along with cosmological parameters does not degrade dark energy constraints if other observational effects are already being considered. The use of priors on nuisance parameters does not seem to affect the dark energy constraints, unless these priors are better than 1\\%.The WaZp cluster finder was run on a cosmological simulation, producing a cluster catalog. Comparing the detected galaxy clusters to the dark matter halos, the observational effects were investigated and measured. Using these measurements, we were able to include corrections for the prediction of cluster counts, resulting in a good agreement with the detected cluster abundance. The results and tools developed in this thesis can provide a framework for the analysis of galaxy clusters for cosmological purposes. Several codes were created and tested along this work, among them are an efficient code to compute theoretical predictions of halo abundance and covariance, a code to estimate the abundance and covariance of galaxy clusters including multiple observational effects and a pipeline to match and compare halo/cluster catalogs. This pipeline has been integrated to the Science Portal of the Laboratório Interinstitucional de e-Astronomia (LIneA) and is being used to automatically assess the quality of cluster catalogs produced by the Dark Energy Survey (DES) collaboration and will be used in other future surveys.

Time management and distance evaluation have long been a difficult task for workers and companies. This thesis studies 6712 pothole coordinates in Gävle municipality, and evaluates the minimal total road distance needed to visit each pothole once, and return to an initial pothole. Road distance is approximated using the flight distance and a simple random sample of 113 road distances from Google Maps. Thereafter, the data from the sample along with a Bayesian approach is used to find a distribution of the ratio between road distance and flight distance. Lastly, a solution to the shortest distance is devised using the Nearest Neighbor algorithm (NNA) and Simulated Annealing (SA). Computational work is performed with Markov Chain Monte Carlo (MCMC). The results provide a minimal road distance of 717 km. / Tidshantering och distansutvärdering är som regel en svår uppgift för arbetare och företag. Den här uppsatsen studerar 6712 potthål i Gävle kommun, och utvärderar den bilväg som på kortast sträcka besöker varje potthål och återgår till den ursprungliga startpunkten. Bilvägsavståndet mellan potthålen uppskattas med hjälp av flygavståndet, där ett obundet slumpmässigt urval av 113 bilvägsavstånd mellan potthålens koordinatpunkter dras. Bilvägsdistanser hittas med hjälp av Google Maps. Därefter används data från urvalet tillsammans med en bayesiansk modell för att hitta en fördelning för förhållandet mellan bilvägsavstånd och flygavstånd. Slutligen framförs en lösning på det kortaste bilvägsavståndet med hjälp av en Nearest Neighbour algoritm (NNA) samt Simulated Annealing (SA). Statistiskt beräkningsarbete utförs med Markov Chain Monte Carlo (MCMC). Resultaten ger en kortaste bilvägssträcka på 717 km.

<p>Graphs are a natural choice for understanding the associations between variables, and assuming a probabilistic embedding for the graph structure leads to a variety of graphical models that enable us to understand these associations even further. In the realm of high-dimensional data, where the number of associations between interacting variables is far greater than the available number of data points, the goal is to infer a sparse graph. In this thesis, we make contributions in the domain of Bayesian graphical models, where our prior belief on the graph structure, encoded via uncertainty on the model parameters, enables the estimation of sparse graphs.</p> <p><br></p> <p>We begin with the Gaussian Graphical Model (GGM) in Chapter 2, one of the simplest and most famous graphical models, where the joint distribution of interacting variables is assumed to be Gaussian. In GGMs, the conditional independence among variables is encoded in the inverse of the covariance matrix, also known as the precision matrix. Under a Bayesian framework, we propose a novel prior--penalty dual called the `graphical horseshoe-like' prior and penalty, to estimate precision matrix. We also establish the posterior convergence of the precision matrix estimate and the frequentist consistency of the maximum a posteriori (MAP) estimator.</p> <p><br></p> <p>In Chapter 3, we develop a general framework based on local linear approximation for MAP estimation of the precision matrix in GGMs. This general framework holds true for any graphical prior, where the element-wise priors can be written as a Laplace scale mixture. As an application of the framework, we perform MAP estimation of the precision matrix under the graphical horseshoe penalty.</p> <p><br></p> <p>In Chapter 4, we focus on graphical models where the joint distribution of interacting variables cannot be assumed Gaussian. Motivated by the quantile graphical models, where the Gaussian likelihood assumption is relaxed, we draw inspiration from the domain of precision medicine, where personalized inference is crucial to tailor individual-specific treatment plans. With an aim to infer Directed Acyclic Graphs (DAGs), we propose a novel quantile DAG learning framework, where the DAGs depend on individual-specific covariates, making personalized inference possible. We demonstrate the potential of this framework in the regime of precision medicine by applying it to infer protein-protein interaction networks in Lung adenocarcinoma and Lung squamous cell carcinoma.</p> <p><br></p> <p>Finally, we conclude this thesis in Chapter 5, by developing a novel framework to compute the marginal likelihood in a GGM, addressing a longstanding open problem. Under this framework, we can compute the marginal likelihood for a broad class of priors on the precision matrix, where the element-wise priors on the diagonal entries can be written as gamma or scale mixtures of gamma random variables and those on the off-diagonal terms can be represented as normal or scale mixtures of normal. This result paves new roads for model selection using Bayes factors and tuning of prior hyper-parameters.</p>

La progression d’un individu au travers d’un environnement diversifié dépend des informations visuelles qui lui permettent d’évaluer la taille, la forme ou même la distance et le temps de contact avec les obstacles dans son chemin. Il peut ainsi planifier en avance les modifications nécessaires de son patron locomoteur afin d’éviter ou enjamber ces entraves. Ce concept est aussi applicable lorsque le sujet doit atteindre une cible, comme un prédateur tentant d’attraper sa proie en pleine course. Les structures neurales impliquées dans la genèse des modifications volontaires de mouvements locomoteurs ont été largement étudiées, mais relativement peu d’information est présentement disponible sur les processus intégrant l’information visuelle afin de planifier ces mouvements. De nombreux travaux chez le primate suggèrent que le cortex pariétal postérieur (CPP) semble jouer un rôle important dans la préparation et l’exécution de mouvements d’atteinte visuellement guidés. Dans cette thèse, nous avons investigué la proposition que le CPP participe similairement dans la planification et le contrôle de la locomotion sous guidage visuel chez le chat. Dans notre première étude, nous avons examiné l’étendue des connexions cortico-corticales entre le CPP et les aires motrices plus frontales, particulièrement le cortex moteur, à l’aide d’injections de traceurs fluorescents rétrogrades. Nous avons cartographié la surface du cortex moteur de chats anesthésiés afin d’identifier les représentations somatotopiques distales et proximales du membre antérieur dans la partie rostrale du cortex moteur, la représentation du membre antérieur située dans la partie caudale de l’aire motrice, et enfin la représentation du membre postérieur. L’injection de différents traceurs rétrogrades dans deux régions motrices sélectionnées par chat nous a permis de visualiser la densité des projections divergentes et convergentes pariétales, dirigées vers ces sites moteurs. Notre analyse a révélé une organisation topographique distincte de connexions du CPP avec toutes les régions motrices identifiées. En particulier, nous avons noté que la représentation caudale du membre antérieur reçoit majoritairement des projections du côté rostral du sillon pariétal, tandis que la partie caudale du CPP projette fortement vers la représentation rostrale du membre antérieur. Cette dernière observation est particulièrement intéressante, parce que le côté caudal du sillon pariétal reçoit de nombreux inputs visuels et sa cible principale, la région motrice rostrale, est bien connue pour être impliquée dans les fonctions motrices volontaires. Ainsi, cette étude anatomique suggère que le CPP, au travers de connexions étendues avec les différentes régions somatotopiques du cortex moteur, pourrait participer à l’élaboration d’un substrat neural idéal pour des processus tels que la coordination inter-membre, intra-membre et aussi la modulation de mouvements volontaires sous guidage visuel. Notre deuxième étude a testé l’hypothèse que le CPP participe dans la modulation et la planification de la locomotion visuellement guidée chez le chat. En nous référant à la cartographie corticale obtenue dans nos travaux anatomiques, nous avons enregistré l’activité de neurones pariétaux, situés dans les portions des aires 5a et 5b qui ont de fortes connexions avec les régions motrices impliquées dans les mouvements de la patte antérieure. Ces enregistrements ont été effectués pendant une tâche de locomotion qui requiert l’enjambement d’obstacles de différentes tailles. En dissociant la vitesse des obstacles de celle du tapis sur lequel le chat marche, notre protocole expérimental nous a aussi permit de mettre plus d’emphase sur l’importance de l’information visuelle et de la séparer de l’influx proprioceptif généré pendant la locomotion. Nos enregistrements ont révélé deux groupes de cellules pariétales activées en relation avec l’enjambement de l’obstacle: une population, principalement située dans l’aire 5a, qui décharge seulement pendant le passage du membre au dessus del’entrave (cellules spécifiques au mouvement) et une autre, surtout localisée dans l’aire 5b, qui est activée au moins un cycle de marche avant l’enjambement (cellules anticipatrices). De plus, nous avons observé que l’activité de ces groupes neuronaux, particulièrement les cellules anticipatrices, était amplifiée lorsque la vitesse des obstacles était dissociée de celle du tapis roulant, démontrant l’importance grandissante de la vision lorsque la tâche devient plus difficile. Enfin, un grand nombre des cellules activées spécifiquement pendant l’enjambement démontraient une corrélation soutenue de leur activité avec le membre controlatéral, même s’il ne menait pas dans le mouvement (cellules unilatérales). Inversement, nous avons noté que la majorité des cellules anticipatrices avaient plutôt tendance à maintenir leur décharge en phase avec l’activité musculaire du premier membre à enjamber l’obstacle, indépendamment de sa position par rapport au site d’enregistrement (cellules bilatérales). Nous suggérons que cette disparité additionnelle démontre une fonction diversifiée de l’activité du CPP. Par exemple, les cellules unilatérales pourraient moduler le mouvement du membre controlatéral au-dessus de l’obstacle, qu’il mène ou suive dans l’ordre d’enjambement, tandis que les neurones bilatéraux sembleraient plutôt spécifier le type de mouvement volontaire requis pour éviter l’entrave. Ensembles, nos observations indiquent que le CPP a le potentiel de moduler l’activité des centres moteurs au travers de réseaux corticaux étendus et contribue à différents aspects de la locomotion sous guidage visuel, notamment l’initiation et l’ajustement de mouvements volontaires des membres antérieurs, mais aussi la planification de ces actions afin d’adapter la progression de l’individu au travers d’un environnement complexe. / When progressing through a varied environment, an individual will depend on visual information to evaluate the size, shape or the distance and time to contact of objects in his path. This will allow him to plan in advance the gait requirements necessary to avoid or step over these obstacles. This concept is also applicable in situations where the subject must reach a target, as with a predator chasing down its prey. The neural structures involved in generating voluntary gait modifications during locomotion have been extensively studied, but relatively little information is available on the processes that integrate visual information to plan these movements. Numerous studies in the primate suggest that the posterior parietal cortex (PPC) plays an important role in the preparation and execution of visually-guided reaching movements. In this thesis, we investigated the proposition that the PPC is similarly involved in the planning and control of visually-guided locomotion in the cat. Our first study examined the extent of cortico-cortical connections between the PPC and the more frontal motor areas, particularly the motor cortex, using injections of fluorescent retrograde tracers. We mapped the cortical surface of anaesthetized cats to identify the somatotopical representations of the distal and proximal forelimb in the rostral portion of the motor cortex, the forelimb representation in the caudal motor area, and also the hindlimb representation. The injection of different tracers in two selected regions, for every cat, allowed us to visualize the density of divergent and convergent parietal projections to these motor sites. Our analysis revealed a distinct topographical organization of parietal connections with all of the identified motor regions. In particular, the caudal motor representation of the forelimb primarily received projections from the rostral bank of the parietal cortex, while the caudal portion of the PPC strongly projected to the rostral forelimb representation. The latter observation is particularly interesting, since the caudal bank of the PPC receives numerous visual inputs and its target, the rostral motor region, is well-known for its involvement in voluntary motor functions. Therefore, this study suggests that the PPC, through extensive connections with the different somatotopic representations of the motor cortex, could constitute an ideal neural substrate for processes such as inter- and intra-limb coordination, as well as the modulation of visually-guided voluntary movements. Our second study tested the hypothesis that the PPC participates in the modulation and planning of voluntary gait modifications during locomotion in the cat. Using the cortical mapping established in our anatomical study, we recorded the activity of parietal neurons, localized in parts of areas 5a and 5b which are known to project strongly towards motor regions involved in forelimb movements. These recordings were obtained during a locomotion task requiring the cat to step over several obstacles of different sizes. By dissociating the speed of the obstacles from that of the treadmill onto which the cat is walking, our experimental protocol also allows us to increase the importance of visual information from the obstacles and to separate it from the influx of proprioceptive influx generated during locomotion. Our recordings revealed two groups of parietal cells on the basis of their activity in relation with the step over the obstacle: one population, mostly localized in area 5a, discharged solely as the lead forelimb passed over the obstacle (step-related cells), and another group, mainly found in area 5b, that showed significant activity at least one step cycle before the gait modification (step-advanced cells). Additionally, we observed an increase of cell activity in these groups, but particularly in step-advanced cells, when the speed of the obstacles was dissociated from that of the treadmill, demonstrating the growing importance of visual information as the task’s difficulty is increased. Finally, a great number of step-related cells were found to discharge specifically in correlation with muscle activity in the contralateral forelimb, regardless of whether or not it led over the obstacle (limb-specific cells). Inversely, the majority of step-advanced neurons tended to maintain their discharge in phase with the leading limb during the gait modification, independently of its position in relation with the recording site (limb-independent cells). We suggest that this additional disparity indicates diversified functions in PPC activity. For example, limb-specific cells could be involved in modulating the movement of the contralateral forelimb over the obstacle, regardless of its order of passage, while limb-independent neurons could instead specify the type of voluntary movement required to overcome the obstacle. Together, our observations indicate that the PPC can potentially influence the activity of motor centers through extensive cortical networks, and contributes to different aspects of visually-guided locomotion, such as initiation and modulation of voluntary forelimb movements, as well as the planning of these gait modifications to allow an individual to walk through a complex environment.

Le traité De l’âme (DA) et les traités connexes (Parva Naturalia) contiennent les éléments d’une théorie de la phantasia, souvent nommée « imagination », ou « représentation ». Dans ce texte, Aristote affirme à plusieurs reprises qu’il est impossible de penser quoi que ce soit sans phantasia. Le DA contient toutefois peu de précisions quant à la portée de cette affirmation. Ce que cela signifie trouve cependant une élucidation si l’on transfert la théorie de la phantasia à un autre texte, les Seconds Analytiques II, 19, portant sur l’acquisition du premier savoir universel à partir de la perception, et des premiers principes intelligibles. Cette étude se propose d’abord de montrer en quoi la théorie de la phantasia s’applique aux SA, et comment ce texte, lu en regard de la phantasia, peut répondre à la question de savoir ce que cela signifie que l’intellect doit nécessairement s’appuyer sur la phantasia pour penser. / The treaty On the Soul (DA) and the connex treaties (Parva Naturalia) expose a theory of phantasia, often translated as « imagination » or « representation ». In the DA, Aristotle maintains that it is impossible to think without phantasia, yet this text offers little precision on the exact signification of his affirmation. An elucidation may however be found in another text, the Posterior Analytics II, 19, which focuses on the acquisition of knowledge, that is, the first universals implanted by perception and the first intelligible principles. This text, as we will firstly demonstrate, has to be read in the frame of the theory of phantasia, which will show that the acquisition of klowledge depends on phantasia. Thus and secondly, it will be clearer what it means that it is impossible for the intellect to think without phantasia.

L’atrophie corticale postérieure (ACP) est un syndrome clinique assez rare d’apparition insidieuse et d’évolution progressive amenant des difficultés visuelles complexes, associées à une atrophie prédominant dans les régions corticales postérieures, en dépit d’une relative préservation des autres sphères de la cognition. Cependant, cette forme atypique de démence demeure encore mal caractérisée en début d’évolution. L’objectif principal de ce projet est de mieux caractériser sur le plan neuropsychologique l’ACP en début d’évolution. Une étude de cas neuropsychologique approfondie a été réalisée chez un patient de 63 ans atteint d’une ACP débutante (M.T.) présentant initialement des plaintes au niveau de la perception visuelle. Une batterie exhaustive de tests neuropsychologiques a été administrée afin d’évaluer l’ensemble des fonctions cognitives. Une évaluation fonctionnelle en ergothérapie a également été réalisée afin d’évaluer l’ampleur des difficultés dans les activités de la vie quotidienne, ainsi qu’une IRM anatomique haute résolution (3 Teslas). Les résultats de l’évaluation neuropsychologique ont mis en évidence des difficultés relativement sélectives à traiter de l’information visuelle spatiale tridimensionnelle, suggérant sur le plan clinique une atteinte de la voie dorsale. Les résultats de l’imagerie par résonance magnétique (IRM) ont mis en évidence une atrophie prédominant dans la région pariétale, surtout dans l’hémisphère droit, corroborant ainsi les atteintes sur le plan neuropsychologique. Cette étude dans son ensemble contribue à mieux documenter la nature des atteintes cognitives, fonctionnelles et cérébrales dans un syndrome progressif rare. / Posterior cortical atrophy (PCA) is an insidious, rare and progressive clinic syndrome which causes complex visual difficulties, associated with atrophy predominating in posterior cortical areas, despite a relative preservation in other cognitive domains. This unusual type of dementia has been poorly characterized in the very early stage of the disease from a neuropsychological standpoint. The main goal of this project is to better characterize PCA from a neuropsychological and functional perspective in the very early stage of the disease, through a very detailed single case study of a 63 years old patient who presented with slowly progressive difficulties in visual perception. A detailed neuropsychological assessment of patient M.T. was carried out in order to assess his abilities in different cognitive domains. A functional evaluation of his activities of daily living was also carried out. The results of the neuropsychological assessment revealed specific difficulties in processing three-dimensional, visuospatial information, suggesting lesions to the occipitoparietal pathway (dorsal stream). M.T. carried out a high-resolution 3T anatomical MRI, which revealed bi-parietal atrophy, predominating in the right hemisphere. This study helps better documenting the nature of neuropsychological, functional, and neuroanatomical deficits in the very early stage of PCA.

Les figures de neuroanatomie de ce mémoire peuvent être téléchargées en haute résolution. / Une voie neuronale sous-tendant la locomotion induite par la détection d’odorants a été découverte chez la lamproie (Derjean et al., 2010). Le signal olfactif est relayé du bulbe olfactif médian au tubercule postérieur, puis à la région locomotrice mésencéphalique et enfin aux cellules réticulospinales qui activent les réseaux locomoteurs spinaux. Des études récentes démontrent que le bulbe olfactif médian est sous l’influence d’une inhibition GABAergique tonique qui régule les réponses des cellules réticulospinales à la stimulation du nerf olfactif (Daghfous et al., 2013). Des mécanismes de modulation supplémentaires pourraient exister dans le bulbe olfactif de Petromyzon marinus puisqu’il contient aussi des fibres dopaminergiques. Chez tous les vertébrés étudiés, la dopamine joue un rôle important dans le traitement olfactif. Des techniques anatomiques (traçage et immunofluorescence) et physiologiques (enregistrements intracellulaires) ont été utilisées pour étudier la modulation dopaminergique de la voie olfacto-motrice. L’immunofluorescence ciblant la dopamine a révélé des fibres plus nombreuses dans la partie médiane du BO et à proximité de neurones de projection et de fibres olfactives. De plus, aucun corps cellulaire immunopositif n’a été détecté dans le bulbe olfactif. L’enregistrement des réponses synaptiques des cellules réticulospinales à la stimulation du nerf olfactif a été réalisé dans le cerveau isolé in vitro. L’injection locale de dopamine dans le bulbe olfactif médian diminue de moitié l’amplitude de réponse. Sous l’effet d’un antagoniste des récepteurs GABAA dans le bain ou localement dans le bulbe olfactif médian, les dépolarisations soutenues enregistrées sont supprimées par l’injection de dopamine. Cependant, l’injection individuelle ou combinée dans le bulbe olfactif médian d’antagonistes sélectifs des récepteurs D1 ou D2, soit le SCH 23390 et l’éticlopride, demeure sans effet significatif sur les réponses olfacto-motrices, indiquant l’absence d’activité dopaminergique tonique. Pour localiser les neurones responsables de cette modulation, des injections de traceur axonal ont été combinées avec l’immunofluorescence ciblant la dopamine. Des cellules dopaminergiques projetant au BO médian ont été observées dans les noyaux dopaminergiques du tubercule postérieur et de l’hypothalamus périventriculaire. Dans l’ensemble, nos résultats montrent anatomiquement et physiologiquement la présence d’une innervation dopaminergique dans le bulbe olfactif médian qui a une action inhibitrice sur le traitement olfacto-moteur. / A neural substrate underlying odor-evoked locomotion was revealed in lampreys (Derjean et al., 2010), involving a neural pathway extending from the medial part of the olfactory bulb to the posterior tuberculum. The signal is then relayed to the mesencephalic locomotor region and eventually reaches reticulospinal cells that activate the spinal locomotor networks. Recent research in the lab (Daghfous et al., 2013) shows that the medial olfactory bulb, is under a tonic GABAergic inhibition gating reticulospinal cell responses to olfactory nerve stimulation. Additional modulatory mechanisms might exist in the olfactory bulb of Petromyzon marinus as it also contains dopaminergic fibers. In every vertebrate studied to date, dopamine plays an important role in olfactory processing. Anatomical (axonal tracers and immunofluorescence) and physiological (intracellular recordings) techniques were used to investigate the dopaminergic modulation of the olfacto-motor pathway. Dopamine immunofluorescence showed scarce innervation of the olfactory bulb that was most abundant in the medial part and in close vicinity to projection neurons and olfactory nerve fibers. Additionally, no dopamine-immunoreactive cell bodies were detected in the olfactory bulb. Synaptic responses of reticulospinal cells to olfactory nerve stimulation were recorded in the isolated brain. Local injection of dopamine in the medial olfactory bulb induces an almost two-fold decrease of the synaptic responses. When GABAA receptor antagonist GABAzine was also injected in the medial olfactory bulb, the effect of dopamine was much more evident and could suppress large bursts of action potentials. However, D1 (SCH 23390) and D2 (Eticlopride) receptor antagonists injection in the medial olfactory bulb failed to alter the amplitude of reticulospinal cell responses to olfactory nerve stimulation, indicating that this modulation is not tonic. To locate the neurons responsible for this modulation, tracer injections combined with dopamine immunofluorescence were performed. Dopaminergic cells projecting to the medial olfactory bulb were found in the dopaminergic nuclei of the posterior tuberculum and the periventricular hypothalamus. Altogether, our results show anatomically and physiologically the presence of a dopaminergic innervation within the medial olfactory bulb that mediates inhibitory effects on olfacto-motor signaling.

Il a été démontré que l’hétérotachie, variation du taux de substitutions au cours du temps et entre les sites, est un phénomène fréquent au sein de données réelles. Échouer à modéliser l’hétérotachie peut potentiellement causer des artéfacts phylogénétiques. Actuellement, plusieurs modèles traitent l’hétérotachie : le modèle à mélange des longueurs de branche (MLB) ainsi que diverses formes du modèle covarion. Dans ce projet, notre but est de trouver un modèle qui prenne efficacement en compte les signaux hétérotaches présents dans les données, et ainsi améliorer l’inférence phylogénétique. Pour parvenir à nos fins, deux études ont été réalisées. Dans la première, nous comparons le modèle MLB avec le modèle covarion et le modèle homogène grâce aux test AIC et BIC, ainsi que par validation croisée. A partir de nos résultats, nous pouvons conclure que le modèle MLB n’est pas nécessaire pour les sites dont les longueurs de branche diffèrent sur l’ensemble de l’arbre, car, dans les données réelles, le signaux hétérotaches qui interfèrent avec l’inférence phylogénétique sont généralement concentrés dans une zone limitée de l’arbre. Dans la seconde étude, nous relaxons l’hypothèse que le modèle covarion est homogène entre les sites, et développons un modèle à mélanges basé sur un processus de Dirichlet. Afin d’évaluer différents modèles hétérogènes, nous définissons plusieurs tests de non-conformité par échantillonnage postérieur prédictif pour étudier divers aspects de l’évolution moléculaire à partir de cartographies stochastiques. Ces tests montrent que le modèle à mélanges covarion utilisé avec une loi gamma est capable de refléter adéquatement les variations de substitutions tant à l’intérieur d’un site qu’entre les sites. Notre recherche permet de décrire de façon détaillée l’hétérotachie dans des données réelles et donne des pistes à suivre pour de futurs modèles hétérotaches. Les tests de non conformité par échantillonnage postérieur prédictif fournissent des outils de diagnostic pour évaluer les modèles en détails. De plus, nos deux études révèlent la non spécificité des modèles hétérogènes et, en conséquence, la présence d’interactions entre différents modèles hétérogènes. Nos études suggèrent fortement que les données contiennent différents caractères hétérogènes qui devraient être pris en compte simultanément dans les analyses phylogénétiques. / Heterotachy, substitution rate variation across sites and time, has shown to be a frequent phenomenon in the real data. Failure to model heterotachy could potentially cause phylogenetic artefacts. Currently, there are several models to handle heterotachy, the mixture branch length model (MBL) and several variant forms of the covarion model. In this project, our objective is to find a model that efficiently handles heterotachous signals in the data, and thereby improves phylogenetic inference. In order to achieve our goal, two individual studies were conducted. In the first study, we make comparisons among the MBL, covarion and homotachous models using AIC, BIC and cross validation. Based on our results, we conclude that the MBL model, in which sites have different branch lengths along the entire tree, is an over-parameterized model. Real data indicate that the heterotachous signals which interfere with phylogenetic inference are generally limited to a small area of the tree. In the second study, we relax the assumption of the homogeneity of the covarion parameters over sites, and develop a mixture covarion model using a Dirichlet process. In order to evaluate different heterogeneous models, we design several posterior predictive discrepancy tests to study different aspects of molecular evolution using stochastic mappings. The posterior predictive discrepancy tests demonstrate that the covarion mixture +Γ model is able to adequately model the substitution variation within and among sites. Our research permits a detailed view of heterotachy in real datasets and gives directions for future heterotachous models. The posterior predictive discrepancy tests provide diagnostic tools to assess models in detail. Furthermore, both of our studies reveal the non-specificity of heterogeneous models. Our studies strongly suggest that different heterogeneous features in the data should be handled simultaneously.