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The interrelationships between brain, cognition, and behaviour are complex but can be more clearly characterised by studying disorders with an underlying genetic basis. This thesis examined these interrelationships in the context of Williams syndrome (WS), a neurodevelopmental genetic disorder that affects aspects of cognition, behaviour, and brain structure. The principal aims of this thesis were to evaluate the cognitive, behavioural, and neuroanatomical profile of WS individuals and to explore the relationships between aspects of the cognitive and behavioural profile and the neuroanatomical changes that are evident in WS. Three general hypotheses, and 10 specific hypotheses, were postulated as a means of exploring these aims. The first general hypothesis predicted that WS individuals would demonstrate distinct features within their cognitive and behavioural profile. Specifically, it was predicted that WS individuals would show relative strengths on verbal tasks and significant deficits on visuospatial and mathematical tasks, in contrast to control participants who were predicted to show a more even profile. It was also predicted that WS individuals would show evidence of heightened affect in response to music and demonstrate hypersociability as compared to control participants

Thesis (Ph. D.)--University of California, San Diego, 2000. / Vita. Includes bibliographical references (leaves 151-168).

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2006. / Vita. Includes bibliographical references (leaves 161-176).

abstract: In blindness research, the corpus callosum (CC) is the most frequently studied sub-cortical structure, due to its important involvement in visual processing. While most callosal analyses from brain structural magnetic resonance images (MRI) are limited to the 2D mid-sagittal slice, we propose a novel framework to capture a complete set of 3D morphological differences in the corpus callosum between two groups of subjects. The CCs are segmented from whole brain T1-weighted MRI and modeled as 3D tetrahedral meshes. The callosal surface is divided into superior and inferior patches on which we compute a volumetric harmonic field by solving the Laplace's equation with Dirichlet boundary conditions. We adopt a refined tetrahedral mesh to compute the Laplacian operator, so our computation can achieve sub-voxel accuracy. Thickness is estimated by tracing the streamlines in the harmonic field. We combine areal changes found using surface tensor-based morphometry and thickness information into a vector at each vertex to be used as a metric for the statistical analysis. Group differences are assessed on this combined measure through Hotelling's T2 test. The method is applied to statistically compare three groups consisting of: congenitally blind (CB), late blind (LB; onset > 8 years old) and sighted (SC) subjects. Our results reveal significant differences in several regions of the CC between both blind groups and the sighted groups; and to a lesser extent between the LB and CB groups. These results demonstrate the crucial role of visual deprivation during the developmental period in reshaping the structural architecture of the CC. / Dissertation/Thesis / M.S. Computer Science 2013

Objetivo: Avaliar a atrofia do corpo caloso (CC) em pacientes com doença de Alzheimer (DA) e comprometimento cognitivo leve (CCL) e quantificar quais regiões dessa estrutura são mais acometidas nessa doença como uso de técnicas quantitativas de ressonância magnética. Metodologia: O estudo contou com a participação de 75 indivíduos sendo 22 controles normais (CN), 30 com CCL e 23 com DA. O volume total do corpo caloso e suas 3 diferentes sub regiões foram delimitadas em cortes sagitais de imagem de ressonância magnética. Os volumes obtidos foram corrigidos para a variação de volume intracraniano. As mascaras foram co-registradas a mapas de relaxometria e transferência de magnetização para analise quantitativa. Resultados: Encontramos atrofia e redução dos valores de relaxometria e transferência de magnetização nos pacientes do grupo DA. As tres sub regiões do corpo caloso apresentaram redução de volume na doença sendo que a atrofia foi maior nas regiões anteriores. Não encontramos diferença significativa nos parâmetros estudados entre CCL e CN. Conclusões: Embora o corpo caloso esteja envolvido no processo de desconexão cortical presente na doença de Alzheimer seu envolvimento não é precoce. / Objective: To evaluate the atrophy of the corpus callosum (CC) in patients with Alzheimer disease (AD) and mild cognitive impairment (CCL) and quantify which regions of this structure are most affected in this disease as using quantitative MRI techniques. Methodology: The study counted on the participation of 75 individuals being 22 normal controls (CN), 30 with CCL and 23 with AI). The total volume of the corpus callosum and its v 3 different sub regions were delimited in sagittal sections of magnetic resonance imaging. The volumes obtained were corrected for intracranial volume variation. The masks were recorded with maps of relaxometry and transfer of magnetization for quantitative analysis. Results: We found atrophy and reduced values of relaxometry and magnetization transfer in patients in the AD group. The three sub regions of the corpus callosum showed volume reduction in the disease, with atrophy being greater in the anterior region. We found no significant difference in the parameters studied between CCL and CN fit .Conclusions: Although the corpus callosum is involved in the process of cortical detachment present in Alzheimer\'s disease, its involvement is late.

Objetivo: Caracterizar o perfil das habilidades de linguagem (oral e escrita) de indivíduos com Displasia Frontonasal com e sem anomalias do sistema nervoso central. Modelo: Análise perspectiva descrevendo os achados da avaliação de linguagem em indivíduos com sinais clínicos de Displasia Frontonasal. Local de execução: Setor de Genética Clínica, HRAC-USP. Participantes: 14 indivíduos, com faixa etária variável, sendo 9 do gênero feminino e 5 do gênero masculino. O GI constituído por 7 indivíduos com displasia frontonasal isolada e 7 com displasia frontonasal associada a anomalias estruturais do Sistema Nervoso Central. Resultados: No GI, 3 Indivíduos (43%) apresentaram alterações nas habilidades de linguagem (oral e escrita), enquanto que no GII, 5 (71%) apresentaram os mesmos achados Na avaliação complementar, os resultados foram parcialmente concordantes com a avaliação clínica, sendo que 43% do GI apresentaram escores abaixo do esperado e no GII foram 71%. Conclusão: Conclui-se que a DFN associada a anomalias estruturais do SNC, como corpo caloso, apresentam em sua maioria, alterações nas habilidades de linguagem oral e escrita em porcentagem bem maior a DFN isolada. Porém as alterações de linguagem/aprendizagem podem estar associadas a DFN, uma vez que esta afecção apresenta um quadro de características fenotípicas bem distintas. / Objective: To characterize the profile of language skills (oral and written) of patients with frontonasal dysplasia with and without central nervous system anomalies. Model: Analysis perspective describing the findings of the evaluation of language in individuals with clinical features of frontonasal dysplasia. Setting: Genetics Departament, HRAC-USP. Participants: 14 individuals with varying ages, 9 females and 5 males. The GI consist 7 individuals with isolated frontonasal dysplasia and 7 with frontonasal dysplasia associated with central nervous system anomalies. Results: In GI, 3 individuals (43%) showed alterations in language skills (oral and escreita), whereas in GII, five individuals (71%) showed the same results. On supplementary assessment, the findings were consistent to the clinical evaluation, and 43% had scores below in GI and 71% in GII. Conclusions: It is concluded that the FND associated with structural abnormalities of the CNS, such as the corpus callosum, have mostly changes in the skills of oral and written language in a much larger percentage DFN isolated. However the language / learning disabilities may be associated with DFN, since this disease presents with distinct phenotypic characteristics.

Tourette’s is currently considered a neurodevelopmental genetic disorder. Georges Gilles de la Tourette is given primary credit for the diagnoses of the disorder in the late 1800s. Clear answers have been elusive although modern research and improvements to neuroimaging have enabled the causal factors of Tourette’s Disorder (TD) to be examined with greater scrutiny. Currently, there is no known cure or pharmaceutical treatment that has been proven 100% effective for all patients and symptoms of Tourette’s. Anecdotally, there have been recent media and self-reports of people diagnosed with Tourette’s finding relief from their symptoms through involvement in focus-based activities such as video games, athletic endeavors and musical engagement, albeit little empirical evidence exists on these subjects. The author is seeking empirical data showing the influence of musical engagement on the symptoms of Tourette’s. This research does not focus on the receptive activity of listening to music, but engagement. This performance-based music making or engagement can be described as the body being physically involved in the creation and production of music which comes from such activities as playing a musical instrument or singing. This study seeks to answer the question, “does musical engagement influence the symptoms of Tourette’s?” A self-reported survey instrument was generated to question those claiming to be musicians who have been diagnosed with TD to explore what effect engaging in a musical activity has on their symptoms. Participants’ responses to ten questions were analyzed. The survey apex involved a Likert-type scale asking to what extent these musicians experienced changes in their symptoms. One hundred eighty-three (N = 183) respondents rated their perceptions from one to five where one equaled drastic symptoms increase by engaging in a musical activity and five equaled drastic symptoms decrease. The mean response from the scale was 4.45, clearly showing that these musicians with TD experienced a great deal of relief when engaged in their activity. This study presents evidence and support for research into neurodevelopmental and musical training correlations and a strong case for childhood music education as a means to facilitate this training.

Pocket proteins (pRb, p107 and p130) are well studied in the role of regulating cell proliferation by controlling progression through the G1/S phase of the cell cycle. Increasing genetic and anatomical evidence suggests that these proteins also control early differentiation and even later stages of cell maturation including neural migration. However, the multifaceted functions of pocket proteins in the regulation of cell proliferation and cell death has complicated our interpretation of their role during development. As a result, the mechanisms through which pocket proteins regulate neuronal migration and neural maturation remain unknown. Using a pRb and p107 double knock out model, we show that a population of upper layer cortical neurons fails to pass through the intermediate zone into the cortical plate. Importantly, these neurons are born at the appropriate time and have exited the cell cycle. In addition, the role of pocket proteins in radial migration is independent cell death, since this migration defect cannot be rescued by eliminating ectopic cell death through Bax deletion. We also show a novel role of pRb and p107 in development of the dorsal midline and guidance of callosal axons. In the absence of pRb and p107, the structures of the commissural plate are highly disorganized and the callosal axons fail to cross the midline. We identify primary defects in axon extension and expression of multiple guidance cues, which can be observed prior to the disorganization of the midline axon guidance structures. Through the use of in vitro cortical explants and in utero electroporation, we identify defects in the rate of axon extension and directional guidance independent from the midline. In addition, protein levels of Netrin and Neuropilin-1 are decreased in the absence of pRb and p107, which could mediate the function of pocket proteins in guiding callosal axons. Indeed, we identify a previously undescribed population of Netrin expressing cells in the cingulate cortex of control embryos which is lost in the pRb/p107 deficient littermates. We propose that these cells play a significant role in callosal axon guidance during normal development. The results presented in this dissertation define multiple novel roles of pRb and p107 in the regulation of radial migration and axon guidance, independent from the role of these pocket proteins in cell death and proliferation.

Aim. The aim of the present work is to examine and compare brain abnormalities found on magnetic resonance imaging (MRI) in children diagnosed with autism spectrum disorders (ASD) and in children without this diagnosis. In terms of psychopathology, the aim is to evaluate a possible relationship between the MRI findings and the severity of autistic symptomatology. Methods. The research study is based on a retrospective analysis of a sample of patients who attended a diagnostic examination focused on ASD and at the same time underwent brain MRI at the Department of Child Psychiatry of the Second Faculty of Medicine at Charles University and University Hospital Motol between the years 1998 and 2015. For clinical diagnosis of ASD, the International Classification of Diseases, 10th revision (ICD-10), was used. Between 1998 and 1999, the assessment of patients was supported by the Childhood Autism Rating Scale. Starting in 2000, the third version of the Autism Diagnostic Interview - Revised was used for assessments; and from 2012 onwards, the Autism Diagnostic Observation Schedule - Generic was added to the diagnostic procedures. From 1998 to 2015, a total of 489 children were diagnosed with pervasive developmental disorder (404 boys, 85 girls). The mean age in the group was 8.0 ± 4.2 years (range...