Pre-surgical planning for endodontic microsurgery is facilitated by the use of cone beam computed tomography (CBCT). The purpose of this study was to determine whether limited field CBCT accurately predicts buccal cortical plate perforations due to endodontic lesions. Thirty-five roots that underwent microsurgical root end resection were included in this study. Prior to the surgery, 90 voxel CBCTs were taken with a Carestream 9300. The scans were analyzed by an endodontic resident and oral radiologist to determine the presence of a perforation in the buccal plate. These findings were compared to the clinical appearance of the bone. There was a significant relationship between a judgment of perforation made on the basis of CBCT and actual perforation as observed clinically. The CBCT prediction was accurate 83% of the time. A predicted perforation was validated in 88% of the instances and a predicted non-perforation was validated in 75% of the instances.

Environmental events simultaneously transduced by more than one sensory modality underlie multisensory processing in the CNS. While most studies of multisensory processing examine functional effects, none have evaluated the influence of local or columnar circuitry. The goal of the present study is to examine of local features of the ferret lateral rostral suprasylvian sulcus (LRSS), a multisensory cortex. Immunostaining revealed the cytoarchitectonic features of the LRSS: thick supragranular layers, a narrow layer IV, and moderately stained but differentiated infragranular layers. Golgi-Cox techniques were used with light microscopy and digital reconstruction to document neuronal morphology. Among the 90 reconstructed neurons, 4 distinct forms or pyramidal and 2 types of non-pyramidal neurons were found. Measurement of maximal dendritic spread indicates that a cortical column in the LRSS was 250.9 um in diameter. These results describe local features of the LRSS upon which future experiments of intrinsic circuitry will be based.

La théorie standard de la consolidation mnésique postule que le stockage à long terme des souvenirs, initialement dépendant de la formation hippocampique, s’effectuerait par l’intermédiaire d’un dialogue hippocampo-cortical au cours duquel l’hippocampe (HPC) se désengagerait progressivement jusqu’à ce que le néocortex devienne à lui seul capable de sous-tendre le rappel des souvenirs. Plusieurs études réalisées chez l’animal, notamment dans le paradigme du labyrinthe à 5 bras validé par l’équipe, confortent cette théorie. Cependant, une exception à ce mode de consolidation est observée dans la tâche de navigation spatiale du labyrinthe aquatique de Morris pour laquelle l’HPC est impliqué de façon permanente dans le rappel quel que soit l’âge des souvenirs. Cette observation a conduit à relancer le débat sur la validité du modèle standard de la consolidation au profit de la théorie des traces multiples (TTM) qui plaide en faveur d’une implication permanente de l’hippocampe lors du rappel d’informations complexes, de nature spatiale ou épisodique. La résolution de la tâche de navigation pourrait en effet nécessiter une intégration spatiale plus complexe que dans le labyrinthe à 5 bras susceptible d’expliquer l’implication durable de la région hippocampique. Ces observations nous ont amenés à réévaluer la composante spatiale du labyrinthe à 5 bras et à développer un nouvel appareil, le labyrinthe à 7 bras, présentant un certain nombre d’innovations. Dans cet appareil, les animaux doivent apprendre à localiser l’unique bras appâté (mémoire de référence) grâce à l’utilisation d’indices spatiaux. Deux versions du protocole ont été mises au point afin de moduler la demande spatiale de la tâche : une version à point de départ fixe (VPF) et une version à points de départ multiples (VPM) (...) Ces travaux nous conduisent à proposer un modèle de fonctionnement de l’interface hippocampocorticale qui intègre la nature et la complexité des représentations mnésiques comme des éléments modulateurs déterminants de la dynamique du dialogue hippocampo-cortical au cours du processus de consolidation mnésique. / Abstract

La polymicrogyrie est un type de malformation corticale dans laquelle on retrouve un excès de gyrations et une surface corticale irrégulière. La polymicrogyrie peut être provoquée par des causes environnementales ou génétiques. C'est ces dernières auxquelles nous nous sommes intéressés et que nous avons étudié afin d'approfondir nos connaissances sur les bases génétiques de la polymicrogyrie. Nous traitons trois projets qui se situent à trois niveaux de recherche différents : étude d'un gène dont la pathogénicité est établie pour le premier, étude de gènes candidats pour le deuxième et recherche de nouveaux gènes candidats pour le troisième. Dans le premier projet, nous avons réussi à prouver l'implication du gène NHEJ1 dans le développement du cortex cérébral. Nous avons montré, grâce à l'ARN interférence in utero que la dérégulation de Nhej1 chez le rat perturbe la migration neuronale, déclenche un phénomène de mort neuronale massive et désorganise les couches corticales. Dans le deuxième projet, après une étude par hybridation génomique comparative sur puce d'ADN, nous avons identifié une duplication dans la région 1p36 chez un patient présentant une polymicrogyrie bilatérale. Nous avons montré que cette duplication casse le gène ENO1 et diminue son expression. L'expression spatio-temporelle d'ENO1 est en accord avec un rôle de celui-ci pendant le développement cérébral. Nous avons également montré que la diminution de l'expression du gène Eno1 perturbe la migration neuronale radiale. / Polymicrogyria is a cortical malformation characterized by excessive gyration and an irregular cortex surface. Environmental and genetic causes can be responsible for this disorder. Our principal aim was to better understand the genetic basis of polymicrogyria. Three projects were conducted. The first focused on the NHEJ1 gene. Using RNA interference and in utero electroporation, we showed that deregulation of NHEJ1 disrupts neuronal migration, triggers massive neuronal cell death and disorganizes the cortical layers. In the second project, we identified by comparative genomic hybridization microarray, a duplication in the 1p36 region in a patient with bilateral polymicrogyria. We have shown that this duplication breaks the ENO1 gene and reduces its expression. The spatio-temporal expression of ENO1 and the fact that its deregulation disrupts neuronal migration indicates that ENO1 is a good candidate gene for cortical development. Finally, in the third project, we identified by exome sequencing of familial cases of bilateral polymicrogyria, one coding variation in the GABRA3 gene. Our work allowed us to generate new knowledge for several candidate genes for polymicrogyria.

Tactile stimulation, an important physiological component of the sexual experience, has the ability to influence the body’s representation in the brain. The sensory homunculus proposed by Penfield and Rasmussen illustrates the way in which the body is represented within the somatosensory cortex. Due to neuroplasticity, this map has the ability to adapt to differing levels of tactile input. How sexual arousal affects, or is represented by, the sensory homunculus is unknown. The study sought to identify: which body areas, rated by participants, are high in their ability to facilitate sexual arousal; to measure the intensity of the different body areas; and to identify whether the areas of greatest intensity lie adjacent cortically to the genital area thus supporting the hypothesised neuroplasticity of brain functioning. The current study was conducted through an online survey which was completed by volunteers with access to university portal sites, social networking sites and referrals. Sampling was convenient and comprised 208 heterosexual males. Data were treated quantitatively through descriptive (frequencies) and inferential (correlations, rotated factor analysis) statistics. The research findings provide support for the sensory homunculus mapping and suggest that there are three areas (genital, facial and trunk) that facilitate sexual arousal. The ability to facilitate sexual arousal is proposed to lie in the close proximity that these areas have within the three erogenous centres (cortically) as well as co-activation of body areas through perceived erogeneity and physiological proximity. This has important implications for sex therapy for individuals in which feeling in the genital area is lacking.

L’hypodynamie-hypokinésie est une situation correspondant à une diminution de l’activité motrice (hypokinésie) couplée à une diminution des charges corporelles (hypodynamie). Chez l’homme, cette situation est retrouvée lors d’une immobilisation, d’un alitement prolongé, d'un séjour en microgravité, ou lors du vieillissement (syndrome d’immobilité). L’hypodynamie-hypokinésie entraine une sévère altération de la performance motrice, notamment de l’équilibre, de la posture et de la locomotion. Cette altération est due à une dégradation du système musculaire (atrophie, changements phénotypiques), mais également à une modification des propriétés fonctionnelles du cortex sensorimoteur (réorganisation corticale, changements d’excitabilité corticale, modifications morphologiques). Si l’altération du système musculaire est bien décrite dans la littérature, les mécanismes impliqués dans la plasticité corticale restent mal connus. Une meilleure compréhension des systèmes mis en jeu dans l’hypodynamie-hypokinésie permettrait de développer des stratégies de prévention et/ou de récupération chez les patients soumis à cette situation. Dans cette optique, un modèle animal est communément utilisé au laboratoire. Il s'agit du modèle d'élévation du train postérieur pendant 14 jours chez le rat. Ainsi, les charges corporelles, s’exerçant habituellement sur les membres postérieurs, sont prévenues et l’activité musculaire limitée. Ce modèle animal reproduit la plupart des effets de l'hypodynamie-hypokinésie décrits chez l'homme.L’objectif de cette étude a été d’explorer les mécanismes de la réorganisation corticale induite par l’hypodynamie-hypokinésie. Notre intérêt s’est plus particulièrement porté sur l’insulin-like growth factor 1 (IGF-1), une protéine ubiquitaire possédant de nombreux rôles au niveau cérébral. En effet, en se fixant à son récepteur, l’IGF-1, parmi une multitude de phénomènes, stimule l’angiogenèse, la neurogenèse, et participe à la plasticité synaptique. De plus, il est reconnu comme étant un acteur central des effets bénéfiques de l’exercice physique au niveau cérébral.Aussi, dans un premier temps, nous avons déterminé les effets de cette hypoactivité sur l’IGF-1 et les voies de signalisation associées dans plusieurs structures impliquées dans la régulation de la performance motrice (cortex sensorimoteur, striatum, cervelet). Nos résultats montrent une sévère diminution des taux d’IGF-1 et de l’activation de la voie PI3K-AKT, et ce spécifiquement dans le cortex sensorimoteur.Dans un second temps, nous avons voulu déterminer si en maintenant le taux d’IGF-1 pendant toute la durée de l’hypodynamie-hypokinésie, il était possible de prévenir la réorganisation corticale et ses conséquences délétères sur le comportement moteur. Pour cela, dans une première partie, notre étude a porté sur le cortex somesthésique et la sensibilité tactile. Nos résultats montrent que l’IGF-1 prévient partiellement la réorganisation corticale et l’altération de la sensibilité tactile induites par l’hypoactivité. Dans une seconde partie, nous nous sommes intéressés à l’analyse du cortex moteur et de la performance motrice. Il apparait qu’un maintien des taux d’IGF-1 prévient une partie de l’altération du système moteur retrouvée en situation d’hypodynamie hypokinésie. Ainsi, l’ensemble de ces données suggère que la diminution des taux d’IGF-1 observée en condition d’hypoactivité joue un rôle clé dans la réorganisation corticale. De plus, notre étude montre qu’une prévention, même partielle, de cette réorganisation corticale peut induire une amélioration fonctionnelle de la performance motrice. / Hypodynamia-hypokinesia is a condition in which the motor activity (hypodynamia) as well as the weight exerted on the lower limbs (hypokinesia) are reduced. In humans, this condition is induced in immobilization, bed-rest, spaceflight or ageing (immobility syndrome) and is characterized by a chronic reduction in neuromuscular activity. This hypoactivity results in a profound alteration of motor task performances, in particular posture, gait and locomotion. These impairments are due to alterations in the muscular system (atrophy, phenotypic changes), but also to plastic changes in neural functions (cortical reorganization, alterations in cortical excitability, morphologic modifications). While degradation of the muscular system is described in the literature, the mechanisms involved in cortical plasticity are still unclear. A better understanding of the systems involved in hypodynamia-hypokinesia would allow the development of preventive and / or recovery strategies for patients affected by this hypoactivity. In this regard, hindlimb unloading is a disuse rodent model in which the elevation of the hindlimbs, during 14 days, prevents the weight to be normally exerted on the hindlimbs and reduces the normal muscular activity, finally causing hypoactivity. Studies performed on this model have shown that hindlimb unloading and human hypoactivity have similar effects. Today, our interest is turned towards insulin-like growth factor 1 (IGF-1), a ubiquitous protein involved in many cerebral functions. Indeed, IGF-1 is known to improve, inter alia, angiogenesis, neurogenesis and to be involved in synaptic plasticity in the whole brain. Moreover, several publications suggest that IGF-1 might mediate the beneficial effects of exercise on the brain.The aim of this study is to characterize the role of IGF-1 in cortical reorganization induced by hindlimb unloading as well as its functional consequences on motor performance. In the first part of the study, we have determined the effects of hindlimb unloading on IGF-1 level and the impact of its downstream main molecular pathways in motor control (sensorimotor cortex, striatum, cerebellum). Our results indicate that hindlimb unloading induces a decrease in IGF-1 level specifically in the sensorimotor cortex. This alteration is associated to a decrease in activation of the PI3K-AKT pathway. The second part of this study is dedicated to the effects of a restoration of IGF-1 levels, during the whole unloading period, on cortical reorganization and behavioral alterations focusing on sensory cortex and tactile sensory discrimination as well as motor cortex and motor performances. Our results show that treatment with IGF-1 partially prevents cortical reorganization and degradation of tactile sensory discrimination. Additionally, it appears that restoration IGF-1 levels prevent some of the effects of hindlimb unloading on the motor system.Taken together, ours results suggest that the decrease in the level of IGF-1 in the sensorimotor cortex during hindlimb unloading plays a key role in the cortical reorganization induced by hypoactivity. Moreover, our study shows that the prevention of this cortical reorganization, even when partial, can induce functional improvement in motor performance.

Introdução: O implante coclear (IC) amplamente aceito como forma de intervenção e (re) habilitação nas perdas auditivas severas e profundas nas diversas faixas etárias. Contudo observa-se no usuário do IC unilateral queixas como localização e compreensão sonora em meio ao ruído, gerado pelo padrão anormal de estimulação sensorial. A fim de fornecer os benefícios da audição binaural, é preconizado a estimulação bilateral, seja por meio do IC bilateral ou com a adaptação de um aparelho de amplificação sonora individual (AASI) contralateralmente ao IC. Esta última condição é referida como estimulação bimodal, quando temos, concomitantemente dois modos de estimulação: Elétrica (IC) e acústica (AASI). Não há dados suficientes na literatura voltados à população infantil que esclareça ou demonstre o desenvolvimento do córtex auditivo na audição bimodal. Ressalta-se que não foram encontrados estudos em crianças. Objetivo: Caracterizar o PEAC complexo P1, N1 P2 em usuários da estimulação bimodal e verificar se há correlação com testes de percepção de fala. Metodologia: Estudo descritivo de séries de casos, com a realização do PEAC em cinco crianças usuárias da estimulação bimodal, a partir da metodologia proposta por Ventura (2008) utilizando o sistema Smart EP USB Jr da Intelligent Hearing Systems. Foi utilizado o som de fala /da/, apresentado em campo livre. O exame será realizado em três situações: Somente IC, IC e AASI e somente AASI. A análise dos dados dos potenciais corticais foi realizada após a marcação da presença ou ausência dos componentes do complexo P1-N1-P2 por dois juízes com experiência em potenciais evocados. Resultados: Foi obtida a captação do PEAC em todas as crianças em todas as situações de teste, além do que foi possível observar a correlação destes com os testes de percepção auditiva da fala. Foi possível verificar que o registro dos PEAC é um procedimento viável para a avaliação da criança com estimulação bimodal, porém, ainda não há dados suficientes quanto a utilização deste para a avaliação e indicação do IC bilateral. / Introduction: The cochlear implant (CI) is already accepted in the area, as an intervention (re)habilitation in severe and profound hearing loss in different age groups. However, it is observed in the unilateral CI users have complaints such as sound localization and understanding speech in noise. Recent studies with Cortical Auditory Evoked Potential (CAEP) demonstrated the fact that the CI cannot favors the ipsilateral development of the auditory pathway as expected. Therefore, unilateral CI users have an abnormal pattern of sensory stimulation. In this sense, the patient is advised and encouraged as to the fitting of hearing aids (HA) in no-implanted ear, especially in the presence of residual acoustic hearing in order to provide the benefits of binaural hearing. This condition is referred to bimodal hearing, when combining electric stimulation from the CI with acoustic stimulation from the contralateral ear provides to HA. Not enough data in the literature has focused on the child population to clarify or demonstrate the development of the auditory cortex in the bimodal hearing. Objective: To characterize the CAEP complex P1-N1-P2 users of bimodal stimulation and check for correlation with performance on tests of speech perception. Methods: A cross-sectional observational study, with the completion of the CAEP in six children using the Bimodal stimulation, the CAEP recording will be based in the methodology proposed by VENTURA (2008) using the system Smart EP USB Jr Intelligent Hearing Systems. The speech sound / of /, presented in free field, will be used. The potential will be recorded in three situations: monaural hearing (only CI); Bimodal hearing (IC and HA) and monoaural hearing (only HA). The examination will be held in three situations: monaural hearing (only IC); Bimodal hearing (IC and hearing aids) and hearing monaural (only the hearing aid). Data analysis of the cortical potential was performed after the marking of the presence or absence of the components of the N1-P1-P2 complex by two judges experienced in evoked potentials. It was verified that the record of the ECCP is a viable procedure for the assessment of children with bimodal stimulation and can assist in bilateral IC nomination process or the maintenance of bimodal stimulation.

Neste estudo fez-se um levantamento dos valores publicados para o Módulo de Young de amostras de osso cortical, oriundas de diferentes espécies e de ossos que desempenham diferentes funções. Os valores encontrados estão bastante dispersos e, procurando a causa da dispersão, encontrou-se inúmeros fatores. Destacaram-se os mais citados na literatura: velocidade de aplicação da carga; direção em que se ensaia a amostra; porosidade, mineralização e densidade; tamanho das amostras; posição das amostras no osso e microestrutura do osso. Concluiu-se que para o osso cortical, a maior causa da variabilidade no Módulo de Young se deve à orientação das fibras colágenas. Trabalhos mais recentes afirmam que amostras com estrutura plexiform apresentam maiores valores para o Módulo de Young que amostras com estrutura osteonal. Construiu-se um dispositivo (suporte das amostras) adequando-o à norma ASTMD790M86&#9491 com a finalidade de otimizar o ensaio de flexão em três pontos. Os aspectos relevantes da construção foram: distância entre os apoios e forma cilíndrica tanto para os apoios como para a cabeça da cruzeta. Na parte experimental, coletou-se 200 amostras de osso cortical de cinco tíbias bovinas, sendo a medida de cada amostra (2x4x40) mm, aproximadamente. Para a coleta e preservação das amostras tomou-se todos os cuidados preconizados como importantes. As amostras foram retiradas das faces anterior, posterior, lateral, medial, antero-lateral, antero-medial, postero-lateral e postero-medial das diáfises das tíbias num trecho situado entre 0,25L e 0,75L, medidos a partir da extremidade distai, onde L é o comprimento total da tíbia. O tamanho das amostras e as dimensões do suporte para o ensaio de flexão seguiram a norma ASTMD790M86&#9491, indicada para ensaio de plásticos em flexão em três pontos. Com a otimização do ensaio de flexão em três pontos, chegou-se a valores de E compatíveis com os da literatura. Concluiu-se que os valores de E crescem das epífises para a diáfise e que os menores valores aparecem nas faces anterior e posterior das tíbias enquanto que os maiores valores aparecem nas faces lateral e medial. / This study shows a survey of the published values for the Young\'s Modulus of cortical bone samples, from different species and from banes which perform different functions. The values found are very dispersed and, by several factors. The outstanding reasons, in the literature are: strain rate; direction in which the samples is tested; porosity; mineralization and density; sample size; sample position in the bone and the bone\'s microstructure. There is a conclusion that for the cortical bone, the greatest cause of variability in Young\'s Modulus is due to the orientation of the collagen fibers. Recent works state that plexiform samples show greater values for the Young\'s Modulus than osteonal samples. A rack to sustain the samples was built according to the ASTMD970M86&#9491 Standards to optimize the three point bending test. The relevant aspects in the devices building were: the span between the supports and the supports and cross head cylindrical shapes. In the experimental part, 200 cortical bone samples were collected from 5 bovine tibiae, and each sample sizing (2x4x40) mm, approximately. For the samples collecting and embalming all the important cares were taken. The samples were collected from the anterior, posterior, lateral, medial, anterolateral, antero-medial, postero-lateral and postero-medial faces from diaphysis from tibiae in an area between 0.25L and 0.75L, measured from the distal extremity, where L is the total tibiae length. The sample sizes and the rack dimensions for the bending test followed the ASTMD970M86&#9491 Standards, indicated for plastic tests in three point bending. With the three point bending optimizing, the E value found were like the ones in literature. We conclude that the E values enhance from the epiphysis to the diaphysis and that smallest values appear in the anterior and posterior tibiae faces, while the greatest values appear in the lateral and medial faces.

No description available.

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No. of bitstreams: 1 FERNANDA_MAJOLO_TES.pdf: 6002507 bytes, checksum: 764acb66fc06c518428a40b9eb5bdd26 (MD5) Previous issue date: 2018-01-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Malformations of cortical development (MDC) include a wide spectrum of Central Nervous System (CNS) disorders related to a complex process of cortex formation. Focal Cortical Dysplasia (FCD), a common type of MDC, is reported as the most frequent structural brain lesion found in children with refractory epilepsy to drug treatment undergoing surgery. Surgical treatment, with complete resection of the dysplastic lesion, is able to stop the seizure resistant to antiepileptic drugs, improving the individual's quality of life and reducing morbidity. FCD is characterized by multiple types of alterations both in cortical architecture and in cytologic abnormalities and it?s pathogenesis is still unknown. In 2004, Palmini et al. classified DCF according to white matter and cortical layer architecture. Taylor-type FCD is characterized by cortical laminar disorganization and dysplastic neurons, compromising the organization of the cortex into six-layered traditionally known. Understanding the mechanisms of action of neurological diseases has involved the use of animal models. However, in the case of brain development of epileptic syndromes, many decades of study have failed to provide a conclusive insight of their mechanisms. Modeling neurological diseases is especially attractive for the application of induced pluripotent stem cells (iPSCs), making possible to derive specific neurons for in vitro studies, contributing to the investigation of the disease. The aim of the present study was to investigate the possible differences in neurogenesis and neurodifferentiation of iPSCs from fibroblasts of individuals affected by Taylor-type FCD and normal individuals. iPSCs were generated from skin fibroblasts of two FCD individuals and two healthy individuals, to form the control group. The reprogramming was done through the fibroblasts exposure to viral vectors containing the OCT4, KLF4, SOX2, and c-MYC genes and the clones were characterized by immunohistochemistry. iPSCs were neurodifferentiated and analyzed at the 14th, 22nd and 35th days. We also analyzed the brain tissue, fibroblasts and iPSCs cells from the individuals. Through qRT-PCR, the expression of 14 genes involved in the neurodifferentiation process were quantified. These genes are associated to neural migration and differentiation, synaptic aspects and Notch signaling. Both individuals were diagnosed with Taylor-type FCD, more specifically, type IIb. In general, individuals with dysplasia presented alterations in the relative quantification in the most genes analyzed compared to control individuals in all processes and study groups (fibroblasts, brain tissue, iPSCs 8 and neurodifferentiated cells). The genes involved in the neural migration and differentiation processes, as well as synaptic aspects and Notch signaling presented quite altered expressions in dysplastic individuals, with the beginning of the majority processes early, before the physiologically typical period. From the found results, we can infer that during the embryonic period, in the neurogenesis and neurodifferentiation process, individuals affected by the disease, possibly presents neuroblasts more sensitive to stimulus, presenting differences in the development of the Nervous System. These changes may be directly related to dysplastic brain development. This work extends the understanding of embryonic neurodevelopment, open up opportunities to further investigations of the involvement and influence of each genes analyzed in the pathogenesis of FCD, as well as in each mechanism of action involved in the brain development. / As Malforma??es do Desenvolvimento Cortical (MDC) re?nem uma ampla gama de patologias do Sistema Nervoso Central (SNC) relacionadas a um complexo processo de forma??o do c?rtex. A Displasia Cortical Focal (DCF), tipo comum de MDC, ? relatada como a les?o cerebral estrutural mais frequente encontrada em crian?as com epilepsia refrat?ria ao tratamento medicamentoso submetidas ? cirurgia. O tratamento cir?rgico, com a ressec??o completa da les?o displ?sica, ? capaz de cessar a convuls?o resistente a drogas antiepil?ticas, melhorando a qualidade de vida do indiv?duo e diminuindo a morbidade. A DCF ? caracterizada por m?ltiplos tipos de altera??es tanto na arquitetura cortical quanto em anormalidades citol?gicas e sua patog?nese ainda ? desconhecida. Em 2004, Palmini e colaboradores classificaram as DCF de acordo com observa??es na subst?ncia branca e na arquitetura da camada cortical. A DCF do tipo Taylor ? caracterizada por uma desorganiza??o laminar e neur?nios displ?sicos, comprometendo a organiza??o do c?rtex em seis camadas histol?gicas tradicionalmente conhecidas. A compreens?o dos mecanismos de a??o das doen?as neurol?gicas tem envolvido o uso de modelos animais. Por?m, no caso do desenvolvimento cerebral das s?ndromes epil?pticas muitas d?cadas de estudo n?o conseguiram fornecer uma vis?o conclusiva sobre seus mecanismos. Modelar doen?as neurol?gicas ? especialmente atraente para aplica??o das c?lulas pluripotentes induzidas (iPSCs), possibilitando derivar neur?nios espec?ficos do pr?prio paciente para estudos in vitro, contribuindo para a investiga??o da doen?a. O objetivo do presente estudo foi investigar as poss?veis diferen?as na neurog?nese e neurodiferencia??o de iPSCs a partir de fibroblastos de indiv?duos acometidos pela DCF do tipo Taylor e indiv?duos normais. As iPSCs foram geradas a partir de fibroblastos de pele de dois indiv?duos displ?sicos e dois indiv?duos saud?veis, para compor o grupo controle. A reprograma??o se deu atrav?s da exposi??o dos fibroblastos a vetores virais contendo os genes OCT4, KLF4, SOX2, e c-MYC e os clones gerados foram caracterizados por imunohistoqu?mica. As c?lulas iPSCs foram neurodiferenciadas e analisadas nos per?odos de 14, 22 e 35 dias. Tamb?m foram analisados o tecido cerebral, fibroblastos e c?lulas iPSCs dos indiv?duos. Atrav?s de qRT-PCR, a express?o de 14 genes envolvidos no processo de neurodiferencia??o foram quantificados. Estes genes est?o associados a migra??o e diferencia??o neural, 6 aspectos sin?pticos e sinaliza??o Notch. Ambos os indiv?duos foram diagnosticados com DCF do tipo Taylor, mais especificadamente, do tipo IIb. No geral, os indiv?duos displ?sicos apresentaram altera??es na quantifica??o relativa na maioria dos genes analisados comparados aos indiv?duos controle, em todos os processos e grupos de estudo (fibroblastos, tecido cerebral, iPSCs e c?lulas neurodiferenciadas). Os genes envolvidos nos processos de migra??o e diferencia??o neural, aspectos sin?pticos e sinaliza??o Notch apresentaram express?es bastante alteradas nos indiv?duos displ?sicos, com o in?cio da maioria dos processos precoces, antes do per?odo fisiologicamente t?pico. A partir dos resultados encontrados, podemos inferir que durante o per?odo embrion?rio, no processo de neurog?nese e neurodiferencia??o, indiv?duos acometidos pela doen?a, possivelmente possuem neuroblastos mais sens?veis a est?mulos, apresentando diferen?as no desenvolvimento do Sistema Nervoso. Essas altera??es podem estar diretamente relacionadas com a forma??o do c?rebro displ?sico. Este trabalho amplia a compreens?o do neurodesenvolvimento embrion?rio, abrindo portas para futuras investiga??es de forma mais aprofundada sobre o envolvimento e influ?ncia de cada um dos genes analisados na patog?nese da DCF, bem como em cada mecanismo de a??o envolvido na forma??o do c?rebro.