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Excitabilidade cortical motora como preditora de resposta na esquizofrenia / Motor cortical excitability as a response prediction in schizophreniaPedro Caldana Gordon 08 November 2018 (has links)
O desenvolvimento da estimulação magnética transcraniana (EMT) permitiu o estudo de potenciais evocados motores eliciados pela estimulação direta do córtex cerebral de forma não-invasiva. Foi observado que diferentes paradigmas de estimulação cortical por EMT apresentam diferentes padrões de resposta, que posteriormente foram associados ao funcionamento de circuitos corticais GABAérgicos e glutamatérgicos do córtex motor, compondo assim índices de excitabilidade cortical motora (ECM). Ademais, desvios da normalidade de tais índices foram encontrados em diversas condições clínicas, incluindo transtornos mentais como a esquizofrenia. O uso dessas medidas também auxiliou o desenvolvimento da estimulação transcraniana por corrente contínua (ETCC), técnica que se mostrou capaz de produzir efeitos neuromodulatórios no sistema nervoso central de forma segura e com mínimos efeitos adversos. Tal técnica vem apresentando possibilidades terapêuticas promissoras, como por exemplo, tendo sido observado sua eficácia no alívio de alucinações auditivas de indivíduos com esquizofrenia. O uso de ETCC para tratamento de sintomas negativos da esquizofrenia também pode vir a se mostrar uma abordagem eficaz, e a análise da ECM pode auxiliar no entendimento dos seus mecanismos de ação e atuar como possível preditor de resposta terapêutica. O objetivo do presente estudo é avaliar o perfil de ECM em um grupo de indivíduos com esquizofrenia, e as possíveis influências de um protocolo terapêutico utilizando ETCC sobre essas medidas. Com esse objetivo, foi selecionada uma coorte de sujeitos com esquizofrenia que participou em ensaio clínico randomizado e controlado com placebo (estimulação sham), tendo a ETCC como intervenção ativa alvo. A ECM foi mensurada na avaliação inicial dos sujeitos, assim como após a primeira sessão de ETCC, e quando da avaliação de desfecho primário. O protocolo terapêutico de ETCC envolveu a colocação de 2 eletrodos de área 5x7 cm, pólo anódico aplicado sobre região correspondente ao córtex pré-frontal dorsolateral esquerdo e pólo catódico aplicado sobre córtex de transição temporoparietal esquerdo; com intensidade de corrente de 2 mA, aplicada por 20 minutos. Cada sujeito foi submetido a 10 sessões no total. Encontramos que idade se correlacionou com diminuição da inibição intracortical, reproduzindo resultado previamente encontrado em indivíduos saudáveis. Acerca da modulação da ECM após sessão de ETCC, observamos que sujeitos submetidos à intervenção ativa apresentaram aumento da inibição intracortical no hemisfério estimulado, em oposição à ausência de mudança significativa da ECM nos sujeitos que receberam estimulação placebo. Os resultados sugerem que sessão de ETCC, utilizando os parâmetros aplicados neste estudo, levou ao aumento da inibição intracortical. Devido a evidências prévias de déficit de inibição intracortical em pessoas com esquizofrenia, é possível que o fenômeno observado represente mecanismo terapêutico da ETCC. É necessário verificar se tal efeito sobre a ECM acompanha medidas objetivas de resposta clinica. Caso isto se comprove, a ECM pode se tornar um valioso marcador de resposta terapêutica e evolução clinica em pacientes com esquizofrenia / The development of transcranial magnetic stimulation allowed the study of motor evoked potentials by applying direct stimuli to the brain cortex in a non-invasive fashion. Different stimulation protocols were observed to yield different response patterns, which were later associated with the functioning of cortical GABAergic and glutamatergic circuits, assembled as motor cortex excitability indices. Also, deviations from normality of such indices were observed in several clinical conditions, including mental disorders such as schizophrenia. The use of these measurements also helped the development of transcranial direct current stimulation (tDCS), a technique which was shown to promote neuromodulatory effects in central nervous system, with potential treatment applications. This technique has been used with success in the treatment of auditory hallucinations in patients with schizophrenia. The use of tDCS might also be effective in the treatment of negative symptoms of schizophrenia, and motor cortex excitability analysis might be used to clarify its physiological effects and act as a possible treatment response predictor. The aim of the present study is to evaluate the motor cortical excitability profile of individuals with schizophrenia, as well as possible influences of tDCS over these measurements. With this aim, we selected a cohort of subjects with schizophrenia who participated in a randomized placebo controlled clinical trial using transcranial direct current stimulation (and sham stimulation for placebo), and measuring motor cortical excitability during baseline evaluation, after the first stimulation session, and at the time of the primary outcome evaluation. The transcranial direct current stimulation protocol used in the present study involved the use of 2 electrodes of area 5x7 cm, anode placed over the region corresponding to the left dorsolateral prefrontal cortex, and cathode over the left cortical temporoparietal juntion. A current of 2 mA intensity was applied for 20 minutes. Each subject underwent a total of 10 sessions. We found that age was correlated to reduced intracortical inhibition, as has been previously found in healthy subjects. Regarding changes of motor cortical excitability following a transcranial direct current stimulation session, we observed that subjects that received the active stimulation displayed an increase in intracortical inhibition, as opposed to those who received sham stimulation, which did not present with any significant change. Results suggest that transcranial direct current stimulation session, using the parameters described in this study, led to an increase in intracortical inhibition. Given previous evidence of intracortical inhibition deficit in individuals with schizophrenia, it is possible that the observed phenomenon corresponds to a treatment mechanism of the electrical stimulation in this population. This need to be confirmed by comparing such changes in cortical excitability to objective measurements of clinical improvement. In case that is confirmed, measurement of motor cortical excitability may have a valuable application as a marker of treatment response and clinical outcome for patients with schizophrenia
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Recorrência espacial aplicada ao estudo de estados quimeraSantos, Moises Souza 01 March 2018 (has links)
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Previous issue date: 2018-03-01 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / A importância do estudo de estados quimera em redes neuronais reflete no fato destes possuírem uma forte ligação com alguns tipos de anomalias diagnosticadas no cérebro, por exemplo, epilepsia,mal de Parkinson e Alzheimer. Neste trabalho, realizamos um estudo da aplicação dos gráficos de recorrência, em sua versão espacial, na caracterização da coexistência de estados coerentes e incoerentes em sistemas dinâmicos acoplados. Utilizamos um modelo constituído de osciladores de fase para uma primeira abordagem da matriz de recorrência. Nossos resultados
indicam que os diagnósticos quantitativos, baseados no gráfico de recorrência, detectam não só a existência de estados quimera como também estados sincronizados e dessincronizados que por ventura emergem na rede. Sobre esse aspecto, mostramos que a análise via recorrência espacial é superior à utilização do parâmetro de ordem global pós-colapso de estados quimera. Este cenário ocorre em algumas situações onde a rede exibe quimera e esta subitamente desaparece do sistema, que passa a exibir um comportamento sincronizado na frequência de seus osciladores. Neste caso, o parâmetro de ordem global não identifica esta mudança de comportamento sendo necessário uma interpretação via outro diagnóstico. Também utilizamos a rede de conectividade cortical de gato, como forma de acoplamento, e distinguimos duas formas de estados híbridos:
uma quimera com a região incoerente em dinâmica temporal de spikes e outra quimera onde a região incoerente apresenta dinâmica temporal de bursts. Identificamos que este último caso de estados quimera possui maior robustez com relação à perturbação externa aplicada no sistema.Concluímos que a região de quimera com bursts necessita de uma intensidade de perturbação duas vezes superior que a região de spikes para deixar de existir na rede de neurônios. / A importância do estudo de estados quimera em redes neuronais reflete no fato destes possuírem uma forte ligação com alguns tipos de anomalias diagnosticadas no cérebro, por exemplo, epilepsia, mal de Parkinson e Alzheimer. Neste trabalho, realizamos um estudo da aplicação dos gráficos de recorrência, em sua versão espacial, na caracterização da coexistência de estados coerentes e incoerentes em sistemas dinâmicos acoplados. Utilizamos um modelo constituído de osciladores de fase para uma primeira abordagem da matriz de recorrência. Nossos resultados
indicam que os diagnósticos quantitativos, baseados no gráfico de recorrência, detectam não só a existência de estados quimera como também estados sincronizados e dessincronizados que por ventura emergem na rede. Sobre esse aspecto, mostramos que a análise via recorrência espacial é superior à utilização do parâmetro de ordem global pós-colapso de estados quimera. Este cenário ocorre em algumas situações onde a rede exibe quimera e esta subitamente desaparece do sistema, que passa a exibir um comportamento sincronizado na frequência de seus osciladores. Neste caso, o parâmetro de ordem global não identifica esta mudança de comportamento sendo necessário uma interpretação via outro diagnóstico. Também utilizamos a rede de conectividade cortical de gato, como forma de acoplamento, e distinguimos duas formas de estados híbridos:
uma quimera com a região incoerente em dinâmica temporal de spikes e outra quimera onde a região incoerente apresenta dinâmica temporal de bursts. Identificamos que este último caso de estados quimera possui maior robustez com relação à perturbação externa aplicada no sistema.Concluímos que a região de quimera com bursts necessita de uma intensidade de perturbação duas vezes superior que a região de spikes para deixar de existir na rede de neurônios
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Eml1 in radial glial progenitors during cortical development : the neurodevelopmental role of a protein mutated in subcortical heterotopia in mouse and human / Eml1 dans les progéniteurs de la glie radiaire au cours du développement cortical : rôle d'une protéine mutée dans l'hétérotopie sous-corticale chez la souris et l'humainBizzotto, Sara 24 June 2016 (has links)
Le développement du cortex cérébral résulte de processus de prolifération, neurogenèse, migration et différenciation cellulaire qui sont contrôlés génétiquement. Les malformations corticales qui résultent d'anomalies de ces processus sont associées à l'épilepsie et la déficience intellectuelle. Nous avons étudié la souris mutante HeCo (heterotopic cortex), qui présente une hétérotopie sous-cortical bilatérale (neurones présents dans la substance blanche) et nous avons identifié la présence d'une mutation sur le gène Eml1 (Echinoderm Microtubule-associated protein-Like 1). De plus, des mutations du gène EML1 ont été identifiées chez des patients atteints d'une forme sévère et rare d'hétérotopie. Dans le cerveau embryonnaire des souris HeCo, des progéniteurs ont été identifiés en dehors de la zone de prolifération, ce qui représente une nouvelle cause de cette malformation. Nous avons étudié la fonction d'Eml1 dans les progéniteurs de la glie radiaire, qui sont clés au cours de la corticogenèse. Nous avons montré qu'Eml1 se localise dans le fuseau mitotique où elle est susceptible de réguler la dynamique des microtubules. Nos données suggèrent qu'Eml1 peut jouer un rôle dans la régulation de la longueur du fuseau puisque celle-ci est perturbée dans les cellules de la glie radiaire chez la souris HeCo. Ceci pourrait représenter la cause primaire de leur ectopie. Nous avons analysé le nombre et la taille des cellules en métaphase dans la partie apicale de la zone ventriculaire où ont lieu les mitoses. Nous proposons ici de nouveaux mécanismes qui régissent l'organisation des progéniteurs dans la zone ventriculaire au cours du développement cortical normal et pathologique. / The cerebral cortex develops through genetically regulated processes of cellular proliferation, neurogenesis, migration and differentiation. Cortical malformations represent a spectrum of heterogeneous disorders due to abnormalities in these steps, and associated with epilepsy and intellectual disability. We studied the HeCo (heterotopic cortex) mutant mouse, which exhibits bilateral subcortical band heterotopia (SBH), characterized by many aberrantly positioned neurons in the white matter. We found that Eml1 (Echinoderm Microtubule-associated protein-Like 1) is mutated in these mice. Screening of EML1 in heterotopia patients identified mutations giving rise to a severe and rare form of atypical heterotopia. In HeCo embryonic brains, progenitors were identified outside the normal proliferative ventricular zone (VZ), representing a novel cause of this disorder. We studied Eml1 function in radial glial progenitors (RGCs), which are important during corticogenesis generating other subtypes of progenitors and post-mitotic neurons, and serving as guides for migrating neurons. We showed that Eml1 localizes to the mitotic spindle where it might regulate microtubule dynamics. My data suggest a role in the establishment of the steady state metaphase spindle length. Indeed, HeCo RGCs in the VZ showed a perturbed spindle length during corticogenesis, and this may represent one of the primary mechanisms leading to abnormal progenitor behavior. I also analyzed cell number and metaphase cell size at the apical side of the VZ, where mitosis occurs. I thus propose new mechanisms governing normal and pathological VZ progenitor organization and function during cortical development.
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Caracterização e identificação de displasias corticais focais em pacientes com epilepsia refratária através de análise de imagens estruturais de ressonância magnética nuclear / Characterization and identification of focal cortical dysplasia in patients with refractory epilepsy through analysis of structural magnetic resonance imagesSimozo, Fabrício Henrique 11 April 2018 (has links)
A displasia cortical focal (DCF) é uma das causas mais frequentes de epilepsia refratária. Na clínica, diferentes informações são usadas para localizar o foco epileptogênico, mas nenhum método é autossuficiente para evidenciar o local original das crises, associado com a presença da DCF. Embora haja relatos na literatura indicando alterações no padrão de distribuição de tons de cinza e morfologia dos voxels decorrentes da DCF, algumas limitações dos métodos desenvolvidos ainda impedem a utilização clínica. Nossa proposta foi investigar a capacidade de identificar DCF através de análises de espessura cortical e padrões de textura em imagens estruturais de Ressonância Magnética (RM), validando os métodos desenvolvidos a partir uma base de imagens retrospectiva, cujo tecido epileptogênico já havia sido ressecado e a DCF confirmada em análise histológica. A caracterização das DCF foi feita a partir da segmentação automática de tecido cortical saudável em conjunto com a segmentação manual da DCF feita por um especialista, e consiste na geração de mapas de característica e extração de valores de distribuições para comparação em análise estatística. Investigamos também a eficácia da detecção de DCF através do uso de algoritmos de aprendizado de máquina para classificação automática. Obtivemos precisão 0,81 e sensitividade 0,87, colocando o método desenvolvido em par com outros métodos presentes na literatura. Entretanto, foi identificada uma grande dependência do desempenho de métodos de pré-processamento, como corregistro e segmentação automática. / Focal Cortical Dysplasia (FCD) is one of the most frequent causes of refractory epilepsy. In clinical procedures, the information gathered from different techniques is used in order to locate the epileptogenic focus, associated with the presence of FCD. However, there is no self sufficient method to evidence the presence and location of such lesions and especially its extension. Although there are reports indicating change in gray scale intensity patterns and voxel morphology in the presence of DCF, limitations in developed methods still prevent their clinical use. Our proposal was to investigate the capability of identifying FCD through cortical thickness and texture patter analysis in structural MRI images, validating developed methods by utilizing a retrospective base of images from patients that were subjected to surgery, with the FCD being confirmed in histological analysis. Characterization of FCD was achieved from automatic segmentation of healthy cortex and manual segmentation of FCD tissue made by an specialist, and consists in the generation of texture or structural feature maps and comparison of distribution values in healthy or FCD tissue with statistical analysis. We also investigate the efficiency of FCD detection with Machine Learning automatic classification, obtaining precision of 0,81 and sensitivity of 0,87, placing our method on par with other methods in the literature. However, there is a major performance dependency of proposed method with pre-processing steps, like registration and automatic segmentation.
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Estudo clínico e radiográfico dos aspectos morfológicos da cadeia estilo-hióidea em sujeitos com disfunção temporomandibular e dor orofacial / Clinical and radiographic study of the morphology of the stylohyoid complex in patients with Temporomandibular Disorders and Orofacial Pain.Andrade, Kelly Machado de 25 March 2011 (has links)
O conhecimento adquirido sobre a síndrome de Eagle demonstra que sua sintomatologia pode ser confundida muito facilmente com outros tipos de desordens craniomandibulares, principalmente a disfunção temporomandibular (DTMs). A falta de conhecimento sobre a síndrome de Eagle e as alterações morfológicas na cadeia estilo-hióidea podem vir a determinar a execução de tratamentos errôneos em pacientes com a síndrome. O objetivo do estudo foi encontrar uma possível correlação entre a presença de DTMs e o alongamento do processo estilóide e também analisar a existência de associação entre a qualidade óssea mandibular e a presença de calcificação da cadeia estilo-hióidea. Para tanto foram analisados 50 pacientes com DTM, confirmada a partir do RDC/TMD. Foi feito o exame clínico e realizado um questionário com questões direcionadas à síndrome de Eagle. Também foi realizada a documentação radiográfica de cada paciente, composta por: radiografia panorâmica digital, cefalométrica lateral digital, radiografia ântero-posterior digital e radiografias transfaciais digitais para analise da cadeia estilo-hióidea. Para a análise das radiografias foi utilizado o programa computacional Radiocef (Radiomemory, Belo Horizonte, Brasil), onde foram realizados traçados cefalométricos por análise específica, e medidas lineares e ângulares do processo estilóide. Nas radiografias panorâmicas foram realizadas medições bilaterais do comprimento do processo estilóide e realizada a classificação morfológica da cadeia estilo-hióidea (LANGLAIS, 1986). Nas radiografias cefalométricas foram realizadas medições do comprimento e angulação anterior do processo estilóide. Nas radiografias ãntero-posterior foram realizadas as medições bilaterais do ângulo medial do processo estilóide. E nas radiografias transfaciais foram feitas as avaliações nas ATMs. Foi feita também medições do Indice Cortical (IC) bilateralmente nas radiografias panorâmicas. Cada radiografia foi traçada e medida por três vezes, com intervalos de tempo de 1 mês entre as medições, sendo as médias posteriormente analisadas a fim de diluir o erro entre as medidas. Foi realizado a estatística através do Programa Biostat 4.0 e o teste de Pearson (p=0,001). Como resultados, foi encontrada uma incidência de 76% de alongamento do processo estilóide na amostra. Houve correlação positiva para as medidas bilaterais realizadas na radiografias panorâmicas (p<0,001) e também para as medidas de comprimento do processo estilóide realizados nas diferentes tomadas radiográficas panorâmicas e cefalométricas laterais (p<0,001). Não houve correlação significativa entre as medidas de angulação medial realizadas bilateralmente (p=0,0011). Foi encontrado 2 pacientes (4%) com síndrome de Eagle clássica. Não foi encontrada associação positiva entre as medidas de comprimento, angulação do processo estilóide e os sintomas. Foi encontrada diferença estatística entre o IC. Concluiu-se que, há prevalencia de alongamento do processo estilóide em pacientes com DTM. Embora não foi encontrada relação entre as medidas realizadas na cadeia estilo-hióidea com os sintomas de cefaléia, dor orofacial, zumbido e vertigem. / The relationship between temporomandibular disorders and Eagle\'s syndrome occurs due to the similarity of symptoms. The knowledge gained about the Eagle\'s syndrome shows that its symptoms can be very easily confused with other types of craniomandibular disorders and numerous other diseases found in regions of the skull, face and neck. The lack of informations about the Eagle\'s syndrome and the morphological alterations in the stylohyoid complex may come to determine erroneous treatments in patients with the syndrome. The aim of this study was to find a possible correlation between the presence of TMD and elongation of the styloid process and to examine the possible association between mandibular bone quality and calcification of the stylohyoid complex. Therefore, it analyzed 50 patients with TMD, confirmed from the RDC / TMD. Clinical examination was made and carried out a questionnaire aimed at the Eagle syndrome. Was also performed radiographic documentation of each patient, consisting of: digital panoramic radiograph, lateral cephalometric digital radiography, anteroposterior digital radiographs and digital transfacial radiographs. For the analysis of radiographs were used computational Radiocef software (Radiomemory, Belo Horizonte, Brazil), being performed by specific analysis cephalometric tracing, and linear and angular measurements of the styloid process. Panoramic radiographs were made in bilateral measurements of the length of the styloid process and performed the morphological classification of the stylohyoid chain (Langlais, 1986). In cephalometric radiographs were performed measurements of length and angulation of the styloid process earlier. Radiographs anteroposterior measurements were taken of the bilateral medial angle of the styloid process. And radiographs transfacials the assessments were made in ATMs. Each radiograph was traced and measured three times with intervals of one month between the measurements and the averages were then analyzed in order to spread the error between the measurements. Was accomplished through the statistical program Biostat 4.0 and Pearson test (p=0.001). As a result, we found an incidence of 76% elongation / mineralization of the styloid process in the sample. There was a correlation between the bilateral measures taken in panoramic radiographs (p<0.001) and also for measures of length of the styloid process carried out in different panoramic radiographs and lateral cephalometric (p<0.001). There was no significant correlation between measures of medial angulation performed bilaterally (p=0.0011). No positive association was found between the measures of length, angulation of the styloid process and symptoms. It was concluded that there is prevalence of elongated styloid process in patients with TMD. Although no relationship was found between measurements at stylohyoid chain with symptoms of headache, orofacial pain, tinnitus and vertigo.
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Caractérisation multi-site de la distribution osseuse corticale et de l'organisation du réseau trabéculaire du squelette postcrânien de Paranthropus robustus : implications taxonomiques, fonctionnelles et paléobiologiques / Multi-site characterisation of cortical bone distribution and cancellous network organisation in the Paranthropus robustus postcranial skeleton : taxonomic, functional and paleobiological implicationsCazenave, Marine 15 October 2018 (has links)
Le taxon du Pléistocène inférieur Paranthropus robustus, dont l'holotype est le spécimen TM 1517, a été défini en 1938 par le paléontologue R. Broom suite à la découverte d'éléments crâniens et postcrâniens sur le site de Kromdraai, Gauteng, en Afrique du Sud. Depuis, d'autres sites sud-africains ont contribué à l'extension de son hypodigme et fourni la preuve de sa contemporanéité à l'échelle macro-régionale avec des représentants des taxons Australopithecus et Homo. L'identification des hominines étant principalement basée sur l'analyse de la variation morphologique des éléments cranio-dentaires, un enjeu majeur dans l'étude des assemblages fossiles des sites sud-africains concerne donc l'identification et l'attribution taxinomique de restes isolés et/ou fragmentaires du squelette axial et appendiculaire non associés à des éléments cranio-dentaires. Il en résulte que plusieurs aspects fonctionnels et paléobiologiques du squelette postcrânien de P. robustus restent à préciser. Au moyen de la microtomographie à rayons X, de l'imagerie virtuelle et d'analyses quantitatives en deux-trois dimensions, nous avons entrepris un projet de recherche visant à explorer, extraire et les patrons d'organisation endostructurale de spécimens fossiles communément, ou préliminairement, attribués à P. robustus. Sur une base comparative, nous visons à (i) identifier quelques caractéristiques osseuses endostructurales propres à ce taxon, qui pourraient fournir un cadre de référence pour l'attribution de spécimens fossiles isolés; (ii) déconstruire l'environnement biomécanique ayant façonné l'arrangement de l'os cortical et trabéculaire au niveau des articulations du coude, de la hanche et du genou; (iii) évaluer le degré de variation et, dans la mesure du possible, les différences liées au sexe et à l'âge. L'échantillon étudié comprend quatre huméri distaux (TM 1517g, SK 24600, SKX 10924, SKX 34805), cinq fémurs proximaux (SK 82, SK 97, SK 3121, SKW 19, SWT1/LB-2), une patella (SKX 1084), des éléments additionnels échantillonnant l'assemblage TM 1517 (l'ulna proximale TM 1517e, la phalange distale d'hallux TM 1517k) et deux ilia (TM 1605, SK 50) provenant des sites de Kromdraai et Swartkrans. [...] / The Early Pleistocene taxon Paranthropus robustus, represented by the holotype TM 1517, was established in 1938 by the paleontologist R. Broom following the discovery of craniodental and postcranial remains at the cave site of Kromdraai, in Gauteng, South Africa. Since, other Southern African sites have contributed to the extension of its hypodigm, providing evidence for its chronological overlap in the macro-region with representatives of the taxa Australopithecus and Homo. As species identification in the hominin fossil record is commonly based on the comparative assessment of craniodental anatomy and morphological variation, the rarity in the hominin-bearing South African cave assemblages of unambiguously associated craniodental and postcranial remains usually complicates the task of identifying isolated and fragmentary elements from the axial and the appendicular skeleton. Consequently, different functionally- and paleobiologically-related aspects of the P. robustus postcranial skeleton remain poorly known. By means of techniques of high resolution X-ray micro-tomography and virtual imaging coupled with two-three-dimensional quantitative analyses, in this research project we explored, extracted and assessed the patterns of endostructural organisation in some fossil specimens commonly, or tentatively, attributed to P. robustus. On comparative ground, we aim at (i) identifying some endostructural bony features characteristic of this taxon, if any, thus tentatively providing a reference framework for the attribution of isolated fossil specimens; (ii) deconstructing the biomechanical (loading) environment having shaped the cortical and cancellous bone arrangement at the elbow, the hip, and the knee joints; (iii) assessing variation and, whenever possible, sex- and age-related differences. The investigated sample consists of four distal humeri (TM 1517g, SK 24600, SKX 10924, SKX 34805), five proximal femora (SK 82, SK 97, SK 3121, SKW 19, SWT1/LB-2), a patella (SKX 1084), some additional elements from the assemblage labelled TM 1517 (the proximal ulna TM 1517e, the distal hallucial phalanx TM 1517k), and two ilia (TM 1605, SK 50) from the sites of Kromdraai and Swartkrans. [...]
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Characterization of the mechanical behavior of growing bone based on new imaging methods / Caractérisation du comportement mécanique de l'os en croissance à l'aide de nouvelles méthodes d'imagerieSemaan, Marie 12 April 2019 (has links)
De nos jours, l’étude biomécanique des structures osseuses représentent un enjeu pour différents domaines: accidentologie, prise en charge des pathologies osseuses, confort des personnes âgées, conception de prothèses innovantes, etc. Le but de cette thèse est de fournir des valeurs de référence représentatives de la qualité de l'os enfant en caractérisant des propriétés mécaniques et morphométriques du tissu osseux en croissance à différentes échelles. Les propriétés mécaniques ont été mesurées à 2 échelles différentes – mésoscopique et microscopique – selon 2 modalités expérimentales – spectroscopie à résonance ultrasonore et microindentation. Un autre volet de cette thèse concerne le développement d’une procédure d’analyse morphométrique adaptée au tissu osseux pour le traitement d’images obtenues par micro-tomographie (RX). Mieux connaître le tissu osseux juvénile est indispensable pour développer des modèles dédiés et ainsi mieux comprendre les mécanismes pathologiques caractéristiques de l'os en croissance (fracture en bois vert) pour améliorer le diagnostic et adapter les choix thérapeutiques pour les jeunes patients. / Nowadays, the biomechanical study of bone structures is a challenge for different fields: accidentology, management of bone pathologies, comfort for the elderly, design of innovative prostheses, etc. The aim of this thesis is to provide reference values representative of the quality of child bone by characterizing the mechanical and morphometric properties of growing bone tissue at different scales. Mechanical properties were measured at 2 different scales - mesoscopic and microscopic - in 2 experimental modalities – resonant ultrasound spectroscopy and microindentation. Another part of this thesis concerns the development of a morphometric analysis procedure adapted to bone tissue for the treatment of images obtained by micro-tomography (RX). A better knowledge of juvenile bone tissue is essential to develop dedicated models and thus better understand the pathological mechanisms characteristic of growing bone (greenstick fracture) to improve diagnosis and adapt therapeutic choices for young patients.
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Amyotrophic lateral sclerosis (ALS) associated with superoxide dismutase 1 (SOD1) mutations in British Columbia, Canada : clinical, neurophysiological and neuropathological featuresStewart, Heather G. January 2005 (has links)
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of motor neurons and their supporting cells in the brain, brainstem and spinal cord, resulting in muscle paresis and paralysis including the bulbar (speech, chewing, swallowing) and respiratory muscles. The average age at onset is 55 years, and death due to respiratory failure occurs 2-5 years after symptom onset in ~ 85% of cases. Five to 10% of ALS is familial, and about 20% of familial cases are associated with mutations in the superoxide dismutase 1 (SOD1) gene. To date, 118 SOD1 mutations have been reported worldwide (www alsod.org). All are dominantly inherited, except for the D90A mutation, which is typically recessively inherited. D90A homozygous ALS is associated with long (~14 years) survival, and some atypical symptoms and signs. The reason for this is not known. In contrast, most other SOD1 mutations are associated with average survival, while some are associated with aggressive disease having lower motor neuron predominance and survival less than 12 months. The A4V mutation, which is the most frequently occurring SOD1 mutation in the United States, is an example of the latter. Understanding the pathogenic mechanisms of SOD1 mutants causing widely different disease forms like D90A and A4V is of paramount importance. Overwhelming scientific evidence indicates that mutations in the SOD1 gene are cytotoxic by a “gain of noxious” function, which although not fully understood results in protein aggregation and loss of cell function. This thesis explores different ALS-SOD1 gene mutations in British Columbia (BC), Canada. Two hundred and fifty-three ALS patients were screened for SOD1 mutations, and 12 (4.7%) unrelated patients were found to carry one of 5 different SOD1 mutations: A4V (n=2); G72C (n=1); D76Y (n=1); D90A (n=2); and 113T (n=6). Incomplete penetrance was observed in 3/12 families. Bulbar onset disease was not observed in the SOD1 mutation carriers in this study, but gender distribution was similar to previously reported studies. Age at symptom onset for all patients enrolled, with or without SOD1 mutations, was older than reported in previous studies. On average, patients with SOD1 mutations experience a longer diagnostic delay (22.6 months) compared to patients without mutations (12 months). Two SOD1 patients were originally misdiagnosed including the G72C patient who’s presenting features resembled a proximal myopathy. Neuropathological examination of this patient failed to reveal upper motor neuron disease. The I113T mutation was associated with variable age of onset and survival time, and was found in 2 apparently sporadic cases. The D76Y mutation was also found in an apparently sporadic case. I113T and D76Y are likely influenced by other genetic or environmental factors in some individuals. Two patients were homozygous for the D90A mutation, with clinical features comparable to patients originally described in Scandinavia. Clinical and electrophysiological motor neuron abnormalities were observed in heterozygous relatives of one D90A homozygous patient. The A4V patients were similar to those described in previous studies, although one had significant upper motor neuron disease both clinically and neuropathologically. Clinical neurophysiology is essential in the diagnosis of ALS, and helpful in monitoring disease progression. A number of transcranial magnetic stimulation (TMS) studies may detect early dysfunction of upper motor neurons when imaging techniques lack sensitivity. Peristimulus time histograms (PSTHs), which assess corticospinal function via recording of voluntarily activated single motor units during low intensity TMS of the motor cortex, were used to study 19 ALS patients having 5 different SOD1 mutations (including 8 of the 12 patients identified with SOD1 mutations from BC). Results were compared with idiopathic ALS cases, patients with multiple sclerosis (MS), and healthy controls. Significant differences were found in corticospinal pathophysiology between ALS patients with SOD1 mutations, idiopathic ALS, and MS patients. In addition, different SOD1 mutants were associated with significantly different neurophysiologic abnormalities. D90A homozygous patients show preserved if not exaggerated cortical inhibition and slow central conduction, which may reflect the more benign disease course associated with this mutant. In contrast, A4V patients show cortical hyper-excitability and only slightly delayed central conduction. I113T patients display a spectrum of abnormalities. This suggests mutant specific SOD1 pathology(s) of the corticospinal pathways in ALS.
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Sleep bruxism is associated with a rise in blood pressureNashed, Angela 04 1900 (has links)
Objectifs : Le bruxisme survenant au cours du sommeil est un trouble du mouvement caractérisé par du grincement de dents et l’activité rythmique des muscles masticateurs (ARMM). Le bruxisme/ARMM est souvent associé à des mouvements du corps et des à éveils corticaux. Une séquence d’activation précède le ARMM/bruxisme. Ces événements incluent une augmentation des variables suivants : l’activité sympathique (-4 minutes), les activités encéphalographique (-4 second), le fréquence cardiaque, l’amplitude de la respiration (-1 second) et l’activité des muscle suprahyoïdiens (-0.8 second). La présente étude a examiné l’association entre le bruxisme et les changements de la pression artérielle.
Méthodes: Dix sujets avec le bruxisme (5 hommes, 5 femmes, âge moyen = 26 ± 1,8) ont complétés 3 nuits de polysomnographie qui comprenait l'enregistrement non invasive de la pression artérielle. La première nuit a servi de dépistage et d’habituation au laboratoire. L'analyse a été réalisée sur les deuxièmes et troisièmes nuits enregistrements. Seuls les épisodes de bruxisme isolés survenant au cours du stade 2 du sommeil ont été utilisés pour l’analyse, pour un total de 65 épisodes. Les mesures des pressions systolique et diastolique ont été prises 20 battements avant et 23 battements après l'apparition de chaque épisode bruxisme lors du sommeil. Les épisodes de bruxisme ont été classés comme suit: 1) bruxisme avec éveil cortical; 2) bruxisme avec mouvement du corps (MC), 3) bruxisme avec éveil cortical et MC. Une quatrième catégorie, bruxisme seul, a également été analysée, mais utilisée comme donnée préliminaire puisque la catégorie se composait de seulement 4 épisodes de bruxisme.
Résultats: Les deux pressions systolique et diastolique ont augmenté avec les épisodes de bruxisme. Cette augmentation a été statistiquement significative pour la pression systolique et diastolique pour les épisodes de bruxisme avec éveil cortical et/ou MC (p ≤ 0,05). L’augmentation moyenne de la pression (systolique / diastolique ± SE) a été : 28,4 ± 2,4/13,2 ± 1,5 mm Hg pour le bruxisme avec éveil cortical; 30,7 ± 1,6/19.4 ± 2.3 mm Hg pour bruxisme avec MC; 26.4 ± 2,8 / 14,6 ± 2.0mm Hg pour bruxisme avec éveil cortical et MC; 22,9 ± 5,2/12,4 ± 3,3mm Hg pour les épisodes de bruxisme seuls.
Conclusion: Le bruxisme du sommeil est associé à des hausses de la pression artérielle pendant le sommeil. Cette hausse est supérieure dans les épisodes de bruxisme associés à un éveil cortical et / ou MC, qui sont souvent associés avec les événements bruxisme. Ces résultats sont en accord avec nos observations antérieures, où le bruxisme est précédé par une augmentation de l'activité sympathique et de la tachycardie sinusale. / Objectives: Sleep Bruxism (SB) is a movement disorder identified by tooth grinding and rhythmic masticatory muscle activity (RMMA). It is often associated with body movements and sleep arousals. Increases in autonomic sympathetic activities that characterize sleep arousal precede SB. These events include an augmentation of the following variables: sympathetic cardiac activity (-4 minutes), electroencephalography frequencies (-4 seconds), heart rate and respiratory amplitude (-1 seconds), and suprahyoid muscle activity (-0.8 seconds). This study examined whether these sympathetic activities are associated with significant changes in arterial blood pressure (BP).
Methods: Ten subjects with SB (5 male; 5 female; mean age ± standard error = 26 ± 1.8) underwent 3 nights of full polysomnography that included non-invasive beat to beat BP recording. The first night served as a screening and habituation night. Analysis was performed on second and third night recordings. Overall analysis was based on single SB episodes occurring in stage 2 sleep only, for a total of 65 episodes. Systolic and diastolic BP measurements were taken from a window of 20 beats before and 23 beats after onset of each SB episode. SB episodes were categorized as: 1) SB + cortical arousal; 2) SB + body movement (BM); 3) SB + cortical arousal + BM. A fourth category, SB alone, was also analysed but used as preliminary data since the category consisted of only 4 episodes.
Results: Both systolic and diastolic BP increased with SB episodes. This increase was significant for both systolic and diastolic BP for SB events with cortical arousal and/or BM (p≤0.05). The average BP surges (systolic/diastolic ± SE) were: 28.4 ± 2.4/13.2 ± 1.5mm Hg for SB + cortical arousal; 30.7 ± 1.6/19.4 ± 2.3mm Hg for SB + BM; 26.5 ± 2.8/14.6 ± 2.0mm Hg for SB + cortical arousal + BM; 22.9 ± 5.2/12.4 ± 3.3mm Hg for SB episodes occurring alone.
Conclusion: Sleep bruxism is associated with blood pressure fluctuations during sleep. This BP surge is greater in SB episodes associated with cortical arousal and/or BM, which often co-occur with SB events. These results are congruent with our previous observations, where SB is preceded by a rise in sympathetic activity and sinus tachycardia.
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Arrêt précoce de la migration neuronale corticale : conséquences cellulaires et comportementales / Premature arrest of cortical neuronal migration : cellular and behavioral consequencesMartineau, Fanny 27 November 2017 (has links)
La migration radiaire est un des processus clefs de la corticogenèse menant à l’établissement d’un cortex en six couches chez les mammifères. La compréhension de ce mécanisme complexe est nécessaire à une meilleure appréhension du développement cortical. Dans ce travail de thèse, j’ai étudié la migration des neurones pyramidaux du cortex sous deux angles distincts. La 1ère partie se place d’un point de vue développemental en appréciant comment le positionnement laminaire résultant d’une migration normale ou anormale affecte la maturation neuronale. La 2nde partie se concentre sur une pathologie migratoire, l’hétérotopie en bande sous-corticale, et les altérations cognitives parfois associées à cette malformation. Pour ces deux projets, la migration neuronale a été altérée chez le rat par knockdown (KD) in utero de la doublecortine (Dcx), un effecteur majeur de la migration. Les neurones positionnés anormalement présentent une orientation incorrecte, un arbre dendritique moins développé, une spinogenère réduite et une altération morpho-fonctionnelle de la synaptogenèse glutamatergique. De plus, notre étude a mis en évidence l’implication de Dcx dans la dendritogenèse et la régulation fine des synapses glutamatergiques in vivo. Enfin, nous avons utilisé les rats Dcx-KD comme modèle d’hétérotopie en bande afin d’étudier comment un déficit de migration neuronale impacte le fonctionnement du cortex. La caractérisation comportementale, réalisée à l’aide d’une large gamme de tests, n’a pas mis en évidence de déficits majeurs des capacités motrices, somatosensorielles ou cognitives chez ces animaux. / Radial migration is one of the key processes leading to the formation of a six-layered cortex in mammals. Understanding this mechanism is necessary to get a better grasp of cortical development. During my PhD, I studied neuronal migration of pyramidal neurons from two different points of views. The 1st part is related to fundamental biology and assesses how laminar misplacement resulting from migration failure influences neuronal maturation. The 2nd one focuses on pathology by investigating a migration disorder, subcortical band heterotopia, and associated cognitive deficits. For both projects, neuronal migration was impaired in rat through in utero knockdown (KD) of doublecortin (Dcx), a major effector of cortical migration. Misplaced neurons display an abnormal orientation, a simplified dendritic arbor, a decreased spinogenesis and morpho-functional alterations of glutamatergic synaptogenesis. Moreover, our study shows that Dcx plays a role in dendritogenesis, in shaping spine morphology and in fine-tuning glutamatergic synaptogenesis. Finally, we used Dcx-KD rats as an animal model of subcortical band heterotopia to assess how migration failure would impact cortical functions. The behavioral characterization carried out through a wide range of tests did not bring to light any major shortcoming regarding motor, somatosensory or cognitive abilities in these animals. Therefore, although Dcx-KD rats display a SBH and develop spontaneous seizures, it does not seem to recapitulate cognitive deficits found in patients.
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