Dissertations / Theses on the topic 'Cortical Morphometry'

Primary Progressive aphasia (PPA) is a disorder characterized by gradual decline in language functions, with relative sparing of other cognitive abilities. This behavioral profile results from neurodegenerative disease that preferentially affects language cortex. As is the case in aphasia resulting from stroke, any of several critical language processing domains may be affected in PPA, including syntax, semantics, phonology, and orthography. In stroke-induced aphasia, traditional lesion mapping approaches have provided important insight into the localization of cortical regions supporting these domains. Specifically, left perisylvian cortex has been implicated in syntactic and phonological aspects of language, whereas left extrasylvian cortical regions are associated with lexical-semantic and orthographic functions. The goal of the present study was to seek converging evidence for the role of left hemisphere cortical regions in language using a voxel-based imaging technique in individuals with PPA. Fifteen individuals with progressive aphasia and fifteen normal controls were given a comprehensive language battery comprising tasks in the domains of syntax, semantics, phonology, and orthography. A subset of patients and all normal controls underwent high-resolution structural MRI scanning. Voxel-based morphometry (VBM) was used to characterize patterns of regional cortical atrophy in the patients relative to controls and to correlate language tasks with gray matter volumes. Results confirm a key role for left perisylvian cortex in phonological and syntactic processes, and indicate that left temporal regions are critically involved in semantic processes. Findings shed light on the veracity of the "primary systems" hypothesis of written language, which posits that written language impairments arise from core cognitive deficits affecting semantic and phonological systems.

It is essential to characterize and quantify naturally occurring morphometric changes in the human brain when investigating the onset or progression of neurodegenerative disorders. The aim of this thesis is to characterize the properties and measure the performance of several popular automated magnetic resonance image analysis tools dedicated to brain morphometry. The thesis begins with an overview of morphometric analysis methods, followed by a literature review focusing on cortical parcellation protocols. Our work identified unanimous protocol weaknesses across all packages in particular issues when addressing cortical variability. The next chapters present a ground truth dataset and a dedicated software to analyse manually parcellated data. The dataset (https://datashare.is.ed.ac.uk/handle/10283/2936) includes 10 healthy middle-aged subjects, whose metrics we used as reference against automated tools. To develop the ground truth dataset, we also present a manual parcellation protocol (https://datashare.is.ed.ac.uk/handle/10283/3148) providing step-by-step instructions for outlining three cortical gyri known to vary with ageing and dementia: the superior frontal gyrus, the cingulate gyrus and the supramarginal gyrus. The software, Masks2Metrics (https://datashare.is.ed.ac.uk/handle/10283/3018), was built in Matlab to calculate cortical thickness, white matter surface area, and grey matter volume from 3D binary masks. Characterizing these metrics allowed further understanding of the assumptions made by software when creating and measuring anatomical parcels. Next, we present results from processing the raw T1-weighted volumes in the latest versions of several automated image analysis tools-FreeSurfer (versions 5.1 and 6.0), BrainGyrusMapping, and BrainSuite (version 13a)- against our ground truth. Tool repeatability for the same system was confirmed as multiple runs yielded identical results. Compared to our ground truth, the closest results were generated by BrainGyrusMapping for volume metrics and by FreeSurfer 6.0 for thickness and surface area metrics. In conclusion, our work sheds light on the significance of clearly detailed parcellation protocols and accurate morphometric tools due to the implications that they both will have. We therefore recommend extra caution when selecting image analysis tools for a study, and the use of independent publicly available ground truth datasets and metrics tools to assist with the selection process.

Prior research has suggested that any cortical volume (CV) abnormalities in Autism Spectrum Disorder (ASD) need to be further explored by examination of the two determinants of CV, that being cortical thickness (CT) and pial surface area (PSA; Murphy, Beecham, Craig, & Ecker, 2011). The current study suggests that the two determinants of CV should be explored even in the presence of null CV findings, if structure-function analyses are significant (i.e., bi-lateral precentral gyrus and neuropsychological motor test) as demonstrated in the current sample (see Duffield et al., 2013). The only significant anatomic finding was reduced CT in the left frontal motor regions (primarily left precentral gyrus), which also corresponded to the only significant relationship between a motor variable (i.e., grooved pegboard test) and motor region-of-interest (ROI) where ASD had a stronger relationship than typically developing controls (TDC; ASD > TDC). Left hemisphere biased CT group differences has been shown to have the highest classification accuracy (i.e., designation of ASD versus TDC) of morphological parameters (Ecker et al., 2010), yet PSA has been shown to have far greater modulation of CV abnormalities. This is particularly true for subthreshold PSA (Ecker et al., 2013). These prior findings are not only consistent with the current motor ROI findings, but also provide an explanatory framework for the functional neuroanatomy of a generally worse left handed performance (i.e., non-dominant hand) for ASD compared to controls in a generally right handed dominant sample (no significant group differences on handedness). The only significant motor ROI finding was in the left hemisphere (i.e., ipsilateral to worse left handed performance), but subthreshold PSA findings in the right precentral were found and likely provide explanatory power of motor performances in the aggregate, despite a lack of significant statistical differences in a specific motor ROI individually.

Magnetic resonance imaging (MRI) is a valuable tool for non-invasively investigating human brain anatomy and functions. The features extracted from MRI data can be used as biomarkers for neurodegenerative diseases, like Dementia. To deeply understand the mechanisms driving the brain changes it is crucial to extract reliable measures from the brain MRI scans and to increase the statistical power by harmonizing different datasets, such as in the ENIGMA studies. Here we applied the ENIGMA-SULCI pipeline to estimate the reliability of the sulcal descriptors extracted across the whole brain and to investigate their correlation with CDR (Clinical Dementia Rating) in the open access dataset OASIS. The OASIS dataset includes T1-weighted acquired from 416 right-handed subjects, for 227 of whose we know CDR. The measurement reliability has been estimated through technical replicates of a subgroup of patients MRI scans. The correlation of each sulcal shape descriptor with the degree of Dementia has been tested through linear regressions between each feature and the CDR series. We have trained linear (regression) and nonlinear (Neural Networks) Machine Learning models in order to classify the subjects in two classes (Dementia and healthy subjects). We got models able to correctly classify more than the 70% of the dataset, starting from sulcal measures.

This thesis is divided into three main parts. In the first, we discuss that, although permutation tests can provide exact control of false positives under the reasonable assumption of exchangeability, there are common examples in which global exchangeability does not hold, such as in experiments with repeated measurements or tests in which subjects are related to each other. To allow permutation inference in such cases, we propose an extension of the well known concept of exchangeability blocks, allowing these to be nested in a hierarchical, multi-level definition. This definition allows permutations that retain the original joint distribution unaltered, thus preserving exchangeability. The null hypothesis is tested using only a subset of all otherwise possible permutations. We do not need to explicitly model the degree of dependence between observations; rather the use of such permutation scheme leaves any dependence intact. The strategy is compatible with heteroscedasticity and can be used with permutations, sign flippings, or both combined. In the second part, we exploit properties of test statistics to obtain accelerations irrespective of generic software or hardware improvements. We compare six different approaches using synthetic and real data, assessing the methods in terms of their error rates, power, agreement with a reference result, and the risk of taking a different decision regarding the rejection of the null hypotheses (known as the resampling risk). In the third part, we investigate and compare the different methods for assessment of cortical volume and area from magnetic resonance images using surface-based methods. Using data from young adults born with very low birth weight and coetaneous controls, we show that instead of volume, the permutation-based non-parametric combination (NPC) of thickness and area is a more sensitive option for studying joint effects on these two quantities, giving equal weight to variation in both, and allowing a better characterisation of biological processes that can affect brain morphology.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
A seleção de animais mais precoces e produtivos, e a melhoria da qualidade do leite são os principais objetivos dos caprinocultores. Com o objetivo de avaliar a interação de dois importantes hormônios, o Cortisol (CORT) e o Fator de Crescimento Análogo à Insulina -1 (IGF-1) na lactação, e suas possíveis influências no desenvolvimento da glândula mamária, produção e qualidade do leite, 38 cabritas (na 1ª fase do experimento) e 24 cabras (na 2ª e 3ª fase do experimento) Saanen divididas em quatro grupos (G1- tratadas com GH e desafiadas com ACTH; G2 – tratadas com GH e desafiadas com placebo; G3 – tratadas com placebo e desafiadas com ACTH; e G4 – tratadas com placebo e desafiadas com placebo). Ao longo de todo experimento foram realizadas coletas de sangue pontuais e durante os desafios, medidas morfométricas internas e externas de úbere e tetos foram realizadas e análises da composição do leite. Não houve diferença no desenvolvimento de úbere e tetos entre animais tratados e não tratados com GH, porém houve maior produção de leite pelos animais tratados, confirmando a eficiência do hormônio em promover maior persistência de lactação. Também houve uma resposta antagônica do IGF-1 ao CORT, durante o desafio das cabras na 3ª fase do experimento, resultado que pode indicar que animais adultos tratados com GH são menos suscetíveis ao estresse que os animais não tratados. O desafio com ACTH e o tratamento com GH não alteraram a composição do leite e a contagem de células somáticas.
The selection of early animals and more productives, and improving the quality of milk are the main goals of goat breeders. With the objective of evaluating the interaction of two important hormones, cortisol (CORT) and the Insulin-Like Growth Factor -1 (IGF-1) in milk, and their possible influences on the development of the mammary gland, yield and quality of milk, 38 kid goats (the 1st. phase of the trial) and 24 goats (in the 2nd and 3rd phase of the trial) Saanen divided into four groups (G1- treated with GH (growth hormone) and challenged with ACTH (adrenocorticotropic hormone), G2 - treated with GH and challenged with placebo; G3 - treated with placebo and challenged with ACTH, and G4 - treated with placebo and challenged with placebo). Throughout experiment samples of blood were collected, internal and external morphometric measures of udder and teats reviews were performed and were performed composition of milk. There were not differences in the development of udder and teats of animals treated and not treated with GH, but treated animals showing higher production than non treated goats, confirming the effectiveness of treatment with GH in promoting increase on persistence of lactation. There was also a response of IGF- 1 antagonist to CORT, the challenge of goats during the 3rd phase of the experiment, result that may indicate that adults treated with GH are less susceptible to stress that the animals not treated. The challenge with ACTH and treatment with GH did not alter the composition of milk and somatic cell count.

Orientador: João Alberto Negrão
Banca: Izabelle Auxiliadora Molina de Almeida Teixeira
Banca: Marco Aurélio de Felício Porcionato
Resumo: A seleção de animais mais precoces e produtivos, e a melhoria da qualidade do leite são os principais objetivos dos caprinocultores. Com o objetivo de avaliar a interação de dois importantes hormônios, o Cortisol (CORT) e o Fator de Crescimento Análogo à Insulina -1 (IGF-1) na lactação, e suas possíveis influências no desenvolvimento da glândula mamária, produção e qualidade do leite, 38 cabritas (na 1ª fase do experimento) e 24 cabras (na 2ª e 3ª fase do experimento) Saanen divididas em quatro grupos (G1- tratadas com GH e desafiadas com ACTH; G2 - tratadas com GH e desafiadas com placebo; G3 - tratadas com placebo e desafiadas com ACTH; e G4 - tratadas com placebo e desafiadas com placebo). Ao longo de todo experimento foram realizadas coletas de sangue pontuais e durante os desafios, medidas morfométricas internas e externas de úbere e tetos foram realizadas e análises da composição do leite. Não houve diferença no desenvolvimento de úbere e tetos entre animais tratados e não tratados com GH, porém houve maior produção de leite pelos animais tratados, confirmando a eficiência do hormônio em promover maior persistência de lactação. Também houve uma resposta antagônica do IGF-1 ao CORT, durante o desafio das cabras na 3ª fase do experimento, resultado que pode indicar que animais adultos tratados com GH são menos suscetíveis ao estresse que os animais não tratados. O desafio com ACTH e o tratamento com GH não alteraram a composição do leite e a contagem de células somáticas.
Abstract: The selection of early animals and more productives, and improving the quality of milk are the main goals of goat breeders. With the objective of evaluating the interaction of two important hormones, cortisol (CORT) and the Insulin-Like Growth Factor -1 (IGF-1) in milk, and their possible influences on the development of the mammary gland, yield and quality of milk, 38 kid goats (the 1st. phase of the trial) and 24 goats (in the 2nd and 3rd phase of the trial) Saanen divided into four groups (G1- treated with GH (growth hormone) and challenged with ACTH (adrenocorticotropic hormone), G2 - treated with GH and challenged with placebo; G3 - treated with placebo and challenged with ACTH, and G4 - treated with placebo and challenged with placebo). Throughout experiment samples of blood were collected, internal and external morphometric measures of udder and teats reviews were performed and were performed composition of milk. There were not differences in the development of udder and teats of animals treated and not treated with GH, but treated animals showing higher production than non treated goats, confirming the effectiveness of treatment with GH in promoting increase on persistence of lactation. There was also a response of IGF- 1 antagonist to CORT, the challenge of goats during the 3rd phase of the experiment, result that may indicate that adults treated with GH are less susceptible to stress that the animals not treated. The challenge with ACTH and treatment with GH did not alter the composition of milk and somatic cell count.
Mestre

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

The side-effects of chemotherapy treatment are an increasingly important research focus as more cancer patients are reaching survivorship. While treatment allows for survival, it can also lead to problems which can significantly affect quality of life. Cognitive impairments after chemotherapy treatment are one such factor. First presented as anecdotal patient reports, over the last decade empirical evidence for this cognitive concern has been obtained. Much attention has been focused on post-chemotherapy research, yet little attention has been granted to these same patients’ cognition before treatment commences. Breast cancer (BC) patients face many obstacles before chemotherapy treatment such as: surgery and side-effects of anesthesia, increased cytokine activity, stress of a new disease diagnosis and upcoming challenges, and emotional burdens such as depression and anxiety. Many of these factors have independently been shown to affect cognitive abilities in both healthy populations as well as other patient groups. Therefore, the pre-treatment (or baseline) BC patient status warrants systematic study. This would then reduce mistakenly attributing carried-over cognitive deficits to side effects of chemotherapy. As well, it is possible that certain confounding variables may have neural manifestations at baseline that could be exacerbated by chemotherapy agents. The following thesis first presents a review paper which critically describes the current literature examining chemotherapy-related cognitive impairments (CRCIs), as well as possible confound variables affecting this population. Subsequently, three original research papers present pre-chemotherapy data showing significant neuroanatomical and neurofunctional differences in BC patients compared to controls. In particular, these neural differences are present in brain regions that have been reported in post-chemotherapy papers. This, as well as the effects of variables such as the number of days since surgery, depression and anxiety scores and more, support the initiative that research attention should increase focus on these patients at baseline in order to better understand their post-chemotherapy results.

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Informática Médica)
Os estudos relacionados com a neuroimagem têm assumido nos últimos anos grande importância por parte da comunidade médica e científica. O aumento da esperança média de vida faz com que se registem cada vez mais doenças do cérebro, das quais as demências e as doenças degenerativas têm assumido especial importância. Na tentativa de perceber quais as alterações anatómicas registadas no cérebro com a idade e aquando do surgimento destas patologias começaram a ser realizados estudos estruturais a este onde a Ressonância Magnética tem-se demonstrado como principal ferramenta para este estudo. Atualmente existem diversas técnicas que possibilitam o estudo estrutural e anatómico do cérebro todavia ainda não existe nenhuma técnica que possibilite o estudo integral de todas as características estruturais do cérebro; no entanto a medição da espessura cortical, volumetria e morfometria baseada em vóxel têm assumido especial preponderância no estudo destas características. O objetivo principal do presente trabalho consistiu em efetuar uma análise por regiões e por vóxeis de forma a perceber quais as regiões cerebrais que eram mais afetadas com a idade no estudo da volumetria, espessura cortical e da área, para isto foram utilizados um método convencional, e o GLMfit para a análise por regiões e o QDEC e o SPM8 para o estudo por vóxeis. Para se poder efetuar os estudos referidos anteriormente foi necessário pré-processar todos os dados em estudo através da utilização da aplicação Freesurfer que possibilitou a correção de pequenos erros originados durante a aquisição das imagens. Com esta dissertação conclui-se que os métodos utilizados para a deteção do comportamento das variáveis em estudo nas análises por regiões se demonstram coerentes entre si e entre os dados bibliográficos consultados, todavia na análise por vóxeis as conclusões não foram tão lineares sendo mesmo impossível efetuar uma comparação entre esses métodos, pois os resultados obtidos foram totalmente distintos.
Studies of neuroimaging have assumed great importance in recent years by the medical and scientific community. The increase in life expectancy increases also the number of brain desease, including dementia and degenerative diseases with particular importance. In order to understand the anatomical alterations caused by aging and these diseases, structural Magnetic Resonance Imaging has proven to be a valuable tool for . Currently there are several techniques that enable structural and anatomical study of the brain However there is still no technique that enables the comprehensive study of all the structural features of the brain, however cortical thickness, volumetric and voxel-based morphometry measurements have assumed particular preponderance in study of these topics. The main objective of this study was to perform an analysis by region and voxel in order to understand which brain regions were affected with aging in term of volumes, cortical thickness and area, so for that were used for a conventional method, and GLMfit for analysis by regions and QDEC and SPM8 for study by voxels. In order to make the studies described above, it was necessary to pre-process all the data in the study by using the FreeSurfer application that enabled the correction of minor errors originated during image acquisition. With this thesis it is possible to conclude that the methods used for the detection of the variables behavior under study are coherent among them and according to the literature, however in the analysis by voxels the findings were not as linear as expected and it was even impossible to performe a comparison between these methods once the results were completely different.

Trabalho de revisão do 6º ano médico com vista à atribuição do grau de mestre (área científica de neurociências) no âmbito do ciclo de estudos de Mestrado Integrado em Medicina.
Retinitis Pigmentosa is a group of hereditary retinal dystrophy disorders associated with progressive visual field loss. In the typical form, retinal degeneration starting at photoreceptors rods in the mid-periphery of the retina causes peripheral visual field defects. Twenty-seven patients and forty healthy controls were examined to determine whether progressive peripheral vision loss in Retinitis Pigmentosa patients with partially preserved vision leads to structural cortical changes. Retinal thickness and retinal nerve fiber layer (RNFL) thickness were assessed with optical coherence tomography (OCT). T1 high-resolution brain anatomical magnetic resonance images from each subject were obtained on a 3-T scanner and processed using SPM8. A whole brain voxel-wise statistical comparison of grey matter volume between the two groups was performed using two different contrasts (controls > patients and patients > controls). Significant statistical difference was found for retinal thickness (P < 0.05), but not for RNFL thickness (p > 0.05) between groups. Grey matter atrophy was observed in the left pericalcarine cortex, cuneus gyrus, posterior cingulate gyrus, right pericalcarine cortex and lingual gyrus (p < 0.001, uncorrected for multiple comparisons, at the whole brain level) of Retinitis Pigmentosa patients. Further analysis with a family-wise error (FWE) correction for multiple comparisons revealed grey matter atrophy in the left pericalcarine cortex, cuneus gyrus and lingual gyrus (p < 0.05). Grey matter hypertrophy was not observed. While the retinal thinning observed is consistent with photoreceptor degeneration, no evidence of structural alteration of RNFL was found. The locations of the grey matter atrophy in visual primary and association cortices are coincident with the profile of peripheral visual field deficit seen in Retinitis Pigmentosa. The cortical atrophy registered is likely to be a result of disuse-driven neuronal atrophy and/or transneuronal degeneration of the visual pathway. These findings may have clinical implications for disease management. A Retinopatia Pigmentar é um grupo de distúrbios hereditários de distrofia da retina associado a perda progressiva de campo visual. Na forma típica, a degeneração da retina que se inicia pelos fotoreceptores bastonetes na médio-periferia da retina causa defeitos periféricos de campo visual. Vinte e sete doentes e quarenta controlos saudáveis foram examinados para determinar se a perda progressiva de visão periférica nos doentes com Retinopatia Pigmentar com visão parcialmente preservada conduz a alterações estruturais corticais. As espessuras da retina e da camada de fibras nervosas da retina (CFNR) foram avaliadas com tomografia de coerência óptica (TCO). As imagens cerebrais anatómicas de ressonância magnética de cada participante foram obtidas num scanner 3-T utilizando a sequência T1 de alta resolução e processadas usando o SPM8. Foi realizada uma comparação estatística voxel-a-voxel do volume de matéria cinzenta entre os dois grupos, examinando todo o cérebro, usando dois contrastes simétricos (controlos > doentes e doentes > controlos). Foi encontrada uma diferença estatística significativa para a espessura da retina entre os grupos (p < 0.05) , mas não para a espessura da CFNR (p > 0.05). Na análise exploratória inicial, foi observada atrofia de matéria cinzenta no córtex pericalcarino esquerdo, giro cúneos, giro cingulado posterior, córtex pericalcarino direito e giro lingual (p < 0.001, com correção apenas para clusters de 100 vóxeis) dos doentes com Retinopatia Pigmentar. Uma análise confirmatória subsequente com correção para comparações múltiplas “family-wise error” (FWE) demonstrou atrofia de matéria cinzenta no córtex pericalcarino esquerdo, giro cúneos e giro lingual (p < 0.05). Não foi observada hipertrofia de matéria cinzenta. Enquanto que a redução da espessura da retina observada é consistente com a degeneração de fotoreceptores, não foi encontrada evidência de alteração estrutural da CFNR. A localização das áreas de atrofia de matéria cinzenta nos córtex visuais primário e de associação coincidem com o perfil de défice periférico de campo visual observado na Retinopatia Pigmentar. A atrofia cortical observada é provavelmente um resultado de atrofia neuronal induzida pelo desuso e/ou degeneração transneuronal da via visual. Estes achados podem ter implicações clínicas no controlo da patologia.

Temporomandibular disorders (TMD) are a family of prevalent chronic pain disorders affecting masticatory muscles and/or the temporomandibular joint. There is no unequivocally recognized peripheral aetiology for idiopathic TMD. The central nervous system (CNS) may initiate and/or maintain the pain in idiopathic TMD due to sustained or long-term nociceptive input that induces maladaptive brain plasticity, and/or to inherent personality-related factors that may reduce the brain's capacity to modulate nociceptive activity. The main aim of this thesis is to determine whether there are structural neural abnormalities in patients with TMD, and whether these abnormalities are related to TMD pain characteristics, or to neuroticism. The specific aims are to delineate in TMD: (1) gray matter (GM) brain abnormalities and the contribution of pain and neuroticism to abnormalities; (2) the contribution of abnormal brain GM aging in focal cortical regions associated with nociceptive processes; and (3) abnormalities in brain white matter and trigeminal nerve and the contribution of pain. In groups of 17 female patients with TMD and 17 age- and sex- matched controls, magnetic resonance imaging revealed that patients with TMD had: (1) thicker cortex in the somatosensory, ventrolateral prefrontal and frontal polar cortices than controls, (2) cortical thickness in motor and cognitive areas that was negatively related to pain intensity, orbitofrontal cortical thickness that was negatively correlated to pain unpleasantness, and thalamic GM volume correlated to TMD duration, (3) an abnormal relationship between neuroticism and orbitofrontal cortical thickness, (4) abnormal GM aging in nociceptive, modulatory and motor areas, (5) widespread abnormalities in white matter tracts in the brain related to sensory, motor and cognitive functions, (6) reduced trigeminal nerve integrity related to pain duration, and (7) abnormal connectivity in cognitive and modulatory brain regions. In sum, this thesis demonstrates for the first time abnormalities in both peripheral nerve and CNS in patients with TMD.

Dissertação de mestrado em Biologia Celular e Molecular, apresentada ao Departamento Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra.
Autism Spectrum Disorder (ASD) is a group of lifelong neurodevelopmental syndromes characterized by impairments in social interaction, communication and by repetitive behaviors and narrow range of interests. Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) studies have detected widespread brain alterations in ASD but a consistent neuropathophysiological characterization is still missing. The great phenotypic and genetic variability present in this spectrum of clinical manifestations suggests the existence of disease-related clusters that warrant careful investigation. We used MRI to measure cortical thickness and subcortical volumes and 1H-MRS to study the neurochemical profile of the anterior cingulate cortex in a homogenous sample of adolescents and adults diagnosed with ASD. With this protocol we intended to identify both anatomical and neurochemical differences that could distinguish between ASD and the control group. We found evidence, in the ASD group, of increased cortical thickness and volume, of cortical and subcortical structures related to the core ASD deficits: automatic and goal-oriented behaviour. Affected cortical regions were manly located in the left hemisphere and have been implicated in social and emotional cognition. Morphometric correlations were also present between striatal structures and regions implicated in language and motor control.
As Perturbações do Espectro do Autismo (PEA) são doenças do neurodesenvolvimento caracterizadas por défices na interacção social, comunicação e por comportamento repetitivos e estereotipados acompanhados por um leque reduzido de interesses e actividades. Estudos com imagem por ressonância magnética (IRM) e espectroscopia de protão por ressonância magnética (EPRM) têm evidenciado alterações cerebrais difusas em pessoas com PEA, no entanto uma caracterização neuropatofisiológica clara ainda não foi encontrada. A grande variabilidade fenotípica e genética encontrada neste espectro de manifestações clínicas, sugere a existência de subpopulações clínicas que é necessário estudar atentamente. Numa população homogénea de adolescentes e adultos com PEA, usámos IRM para medir a espessura cortical e o volume de estruturas subcorticais e usámos EPRM para estudar o perfil neuroquímico do cíngulo frontal. Com esta abordagem quisemos identificar alterações anatómicas e neuroquímicas que nos permitissem distinguir entre o grupo das PEA e o grupo controlo. Foi observado, grupo das PEA, um aumento de espessura cortical e do volume de regiões corticais e subcorticais que têm sido relacionadas com défices no comportamento automático e executivo. As regiões corticais afectadas encontraram-se principalmente do hemisfério esquerdo, estando relacionadas com a cognição social e emocional. Também foram observadas correlações morfométricas entre estruturas pertencentes ao estriado e zonas corticais relacionadas com a linguagem e o controlo motor.

Trabalho final de mestrado integrado em medicina área científica de Neurociências, apresentado á Faculdade de Medicina da Universidade de Coimbra
Neuroimaging studies have proven to be a valuable resource in Huntington’s disease (HD). As an autosomal dominant genetic disorder, it is possible to identify individuals before they manifest clinical symptoms (“prodromal HD”). This study was designed to assess if neuroimaging measures could be useful to successfully distinguish prodromal individuals from previously clinically diagnosed patients. Seven participants with previously clinically diagnosed disease and eight individuals in a presymptomatic state underwent brain magnetic resonance imaging (MRI) and were matched and compared to a group of thirteen healthy controls. Cortical reconstruction and volumetric segmentation was performed with FreeSurfer 5.1. We have found significant statistical differences on Caudate, Putamen and Globus Pallidus, from both hemispheres. Diagnosed group had smaller volumes when compared to Prodromal and Control group. Thickness maps derived from Diagnosed and Control groups’ comparison revealed a thinning pattern affecting mostly the posterior and superior cerebral regions. Our results suggest that structural MRI volumes and thickness maps can be useful to monitor Huntington’s disease progression, allowing researchers to identify individuals in different stages of the disease. Clinical trials might benefit the most, by synergizing the current clinical diagnostic method with MRI measures to track neurodegenerative patterns of HD