Early experience critically shapes cognitive, affective, and behavioral development, and experiences of early life stress (ELS) have been documented to negatively impact developmental trajectories. An increasing need exists for innovative intervention development to ameliorate negative impacts of ELS. Translational neuroscience approaches hold promise for addressing the needs of individuals who have experienced ELS through the development and testing of targeted intervention strategies grounded in neuroscientific knowledge. The current dissertation work employed a translational neuroscience approach to improve inhibitory control (IC) in a group of adolescents (N=20) exposed to a range of ELS via a brief, computerized training paradigm. Baseline analyses of the association between ELS and IC revealed a positive relationship (i.e., increased ELS, increased IC performance), counter to hypotheses. The IC training did not significantly improve IC in the training group compared to the control group over time, contrary to hypotheses and previous work demonstrating the effectiveness of this IC training in young adults. Transfer of training effects to a non-trained IC task and to real-world risk-taking behavior were limited. ELS demonstrated some moderation of neural effects of IC training. The use of neuroimaging in this dissertation work allowed for further investigation of neural mechanisms even in the absence of significant behavioral training, transfer, and moderation effects. Results are discussed in the context of the utility of such IC training approaches for adolescents with ELS exposure and of translational neuroscience approaches more broadly. Future directions for IC training, translational neuroscience intervention approaches, and the incorporation of neuroimaging in this work are explored. This dissertation includes unpublished co-authored material. / 10000-01-01

Adaptation is a fundamental property of the nervous system that underlies the maintenance of successful actions through flexible reconfiguration of sensorimotor processing. The primary aims of this thesis are 1) to investigate the computational and neural underpinnings of sensorimotor memory formation during prism adaptation (PA) in humans, and 2) how they interact with anodal transcranial direct current stimulation (a-tDCS) of the primary motor cortex (M1), in order to 3) improve efficacy of prism therapy for post-stroke spatial neglect. In chapter 4, we modify an influential state-space model of adaptation in order to characterize the contribution of short and long memory timescales to motor behaviour as sensorimotor after-effects (AEs) develop during PA. This enables us, in the multimodal 7 Tesla MRI experiment reported in chapter 5, to demonstrate that the level of M1 excitation:inhibition causally sets the relative contribution of long versus short memory timescales during PA, thus determining behavioural persistence of the AE at retention in young healthy adults. This finding offers a bridge between different levels of investigation by providing a biologically plausible neuro-computational model of how sensorimotor memories are formed and enhanced by a-tDCS. In chapter 6, we use the ageing motor system as a model of reduced GABAergic inhibition and show that the age-related decrease in M1 GABA explains why older adults demonstrate more persistent prism AEs. Taken together, these data indicate that the reduction in M1 GABAergic inhibition via excitatory a-tDCS during PA has the potential to enhance persistence of adaptation memory in both young and older adults. Informed by these results, we subsequently ask whether standard (multi-session) PA therapy combined with left M1 a-tDCS translates to greater and/or longer-lasting clinical improvements in post-stroke spatial neglect patients. In chapter 7, we compare the multimodal neuroimaging data of six neglect patients to normative data of age-matched controls. We show that in all patients, the lesion interrupted long-range frontoparietal connections, and we provide direct evidence for a pathological left dominance of activity within the lateral occipital cortex during deployment of bilateral visuospatial attention. In chapter 8, we present the behavioural performance of these patients throughout the two phases of the clinical study (i.e. before and after either PA + real M1 a-tDCS or PA + sham M1 atDCS). There was no clear effect of a-tDCS on the therapeutic effect of PA in these patients. The results of the studies presented in this thesis provide a novel insight into the neurocomputational mechanisms of sensorimotor memory formation and its modulation by a-tDCS in the healthy brain. Further investigation of how these mechanisms relate to therapeutic improvements following PA in certain neglect patients is needed.

xv, 169 p. ; ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / Improvements in neuroimaging techniques have made it possible to answer questions regarding the neural organization for the processing of syntax in normal participants. In this series of experiments we examined the effects of linguistic proficiency and age of second language acquisition on neural organization for syntactic processing. We examined these factors using two complementary methodologies: event-related potentials (ERPs), which affords a temporal resolution on the order of milliseconds, and functional magnetic resonance imaging (fMRI), with spatial resolution on the order of millimeters. In order to compare results across methodologies, we used an auditory syntactic violation paradigm with similar experimental parameters in each methodology. In Chapter II we examined neural organization for syntactic processing using ERPs in monolingual native speakers of higher and lower proficiency and found that violations elicited an early onset (100 ms) anterior negativity (EOAN) followed by a later positivity (P600) in all participants. Compared to lower proficiency participants, higher proficiency participants showed an EOAN that was more focal spatially and temporally, and showed a larger P600. These results were supported by a correlational analysis of a larger group of monolingual native speakers with a wide range of proficiency scores. This analysis also found a relationship between childhood socioeconomic status and the recruitment of the EOAN over left hemisphere sites, raising the hypothesis that effects of childhood experience may endure into adulthood. In Chapter III we examined the effects of age of acquisition on syntactic processing by recruiting a group of late learners of English who were matched for proficiency with a group of monolingual native speakers from Chapter II. While in native speakers violations elicited a robust EOAN, this effect was absent in the late learner group, suggesting that early language exposure is important for the recruitment of resources reflected in this effect and independently of proficiency. In Chapter IV we gathered ERP and fMRI data from monolingual native speakers and found proficiency differences in the recruitment for syntactic processing of left inferior frontal and posterior regions. We linked proficiency-related modulations in the different ERP syntactic effects to specific fMRI activations indexing syntactic processing. / Adviser: Helen J. Neville

Early life stress (ELS) affects the developing brain and impacts capacity for self-regulation and risk for psychopathology. The high spatial resolution of functional magnetic resonance imaging (fMRI) confers an advantage for studying specific neural regions posited to link ELS with subsequent functioning. The first chapter in this dissertation reviews the literature establishing the feasibility and utility of fMRI research with infants and young children. This chapter examines methodological issues and outlines the potential for this technique to make unique contributions to understanding how ELS influences brain development. The next two chapters present results from a study that employed a functional activation paradigm and resting state functional connectivity MRI (rs-fcMRI) to examine associations between a common source of ELS, non-physical interparental conflict, and neural functioning during infancy. The functional activation paradigm focused on emotional tone of voice as a stimulus relevant to interparental conflict, which is likely salient to infants. Higher levels of interparental conflict (as reported by mothers) were associated with infants (6 to 12 months of age) showing greater reactivity to very angry versus neutral tone of voice in neural regions associated with processing and regulation of stress and emotion (hypothalamus and rostral anterior cingulate cortex). The rs-fcMRI analysis examined coordinated neural functioning in the absence of stimuli, focusing on the amygdala as a key region for understanding the impact of ELS and the posterior cingulate cortex as part of a group of regions that show higher levels of activity in the absence of stimuli (the default network). The results replicate previous work characterizing the default network in infants and provide novel evidence for the functional connectivity of the amydgala and amygdala subregions during infancy. Interparental conflict was associated with variation in the connectivity of both regions. Thus levels of interparental conflict were associated with neural reactivity to a stressor-relevant stimulus and with patterns of coordinated neural functioning in the absence of such stimuli. These results provide support for the utility of using fMRI with infants to examine early emerging associations between common forms of ELS and brain functioning. This dissertation includes previously published and co-authored material. / 2016-10-17

Nos últimos anos, temos nos deparado com a difusão maciça e a popularização crescente de descrições biológicas para aspectos outrora pensados como mentais, sociais, ou relacionais. Visível em diversas arenas leigas e científicas, esta tendência freqüentemente elege o cérebro como o órgão privilegiado da sua atenção. A cada semana é divulgada uma nova localização cerebral correlacionada os mais variados aspectos comportamentais e ou de personalidade. Acompanhando este movimento, é notável o esforço intelectual e financeiro despendido nos últimos anos no campo da saúde mental, no sentido de fazer avançar pesquisas cujo foco central é a descoberta das bases neurobiológicas dos transtornos mentais. Esta tendência apontaria na direção de uma fusão entre a psiquiatria e a neurologia em uma disciplina única, de teor fisicalista, chamada por alguns de cerebrologia. Dentre os acontecimentos que serviram de alicerce para a legitimação e a popularização desta tendência, o desenvolvimento nas últimas décadas de novas técnicas e tecnologias de visualização médica, como a tomografia por emissão de pósitrons (PET scan) e a ressonância magnética funcional (fMRI), foi fundamental. Elas permitiram a construção de imagens das mais diversas categorias nosográficas construídas no campo psiquiátrico, veiculando tacitamente uma série de pressupostos e promessas. Malgrado o imaginário cultural sustentado por estas tecnologias e todo o esforço despendido nas últimas décadas no sentido de se tentar localizar os marcadores biológicos dos transtornos psiquiátricos, não há, até o presente momento, nenhum resultado conclusivo que autorize o diagnóstico por imagem de nosografias como a esquizofrenia, a depressão, e muito menos o jogo patológico. Apesar de todo o alarde midiático e dos montantes milionários direcionados para pesquisas nesta área, os resultados concretos obtidos até agora não estão livres das mais ferozes controvérsias. Entretanto, ainda que estejamos muito longe da construção de mapas precisos para as perturbações mentais é espantoso o poder de convencimento que as neuro-imagens comportam na atualidade. Os scans são exibidos como verdades visuais, ou fatos acerca das pessoas e do mundo, numa proporção muito superior aos dados que apresentam. Alguns críticos chamam este aspecto de neurorealismo, ou de retórica da auto-evidência. A intenção deste trabalho é problematizar o poder persuasivo que as neuro-imagens detém na contemporaneidade, especialmente quando utilizadas com a finalidade diagnóstica no campo da saúde mental. Se estas imagens transmitem uma ideia de neutralidade, transparência imediata e auto-evidência, este trabalho almeja inseri-las num contexto sócio-histórico, a partir do qual puderam adquirir sentido, familiaridade e valor de verdade. O ponto de partida é o de que elas estão localizadas no cruzamento de dois movimentos históricos distintos: o das ilustrações médicas, em sua relação com a produção de conhecimento objetivo; e o das pesquisas acerca da localização no córtex cerebral de comportamentos complexos e traços de personalidade. Além de estabelecer algumas condições históricas de possibilidade para a emergência de um neo-localizacionismo cerebral, mediado pelas novas tecnologias de imageamento, pretende-se enfatizar algumas descontinuidades com projetos anteriores e marcar a influência do contexto cultural da atualidade para o sucesso e poder persuasivo deste tipo de tecnologia. / Lately, we have seen the popularization and massive difusion of biological descriptions to aspects that we used to consider as social or mentaly based. Notable in scientific and lay environments, this tendency frequently chooses the brain as the privileged organ of its attention. Every week, a new cerebral locality, related to behavioral and personality traces, is publicized. Along with this movement, it is remarkable the intellectual and financial efforts undertaken in the last years in the domaine of mental health, to advance the researchs that aim to discover the neurobiological basis of the mental disorders. This tendency points to the fusion between psychiatry and neurology in only one discipline, phisicalistically based, sometimes called brainology. One of the most important events that served as a base to the legitimation and the popularization of this trend was the development, in the last decades, of the new medical imaging techniques and technologies, like the Positron Emission Tomography (PET scan) and the Functional Magnetical Ressonance Imaging (fMRI). These technologies allowed the image construction of almost every nosografic category made up in the psychiatric domaine, transmitting implicitly many assumptions and promises. Notwithstanding the cultural imaginary sustaned by these technologies and the efforts undertaken to localize the biological markers of psychiatric disorders, there isnt, until the present time, any conclusive result that entitle the imaging diagnostic of nosographies like schizophrenia, depression, and the pathogical gambling. In spite of the mediatic attention and the milionaires amounts destined to researchs in this field, the concret results obtained until now arent free from tough controversies. However, even considering we are very far from the construction of accurate maps for the mental disfunctions, its incredible the power of conviction that neuroimages have nowadays. The scans are exhibited as visuable truths, or facts concerning the people and the world, in a proportion much superior to the data they present. Some critics call such an aspect neurorealism, or rhetoric of auto-evidence. The aim of this work is to question the persuasive power acquired by the neuroimages nowadays, especially when addopted to diagnostic aims in the field of mental health. If these images pass the idea of neutrality, immediate transparence and auto-evidence, this work intends to include them in a social-historical context, through wich they have obtained meaning, familiarity, and the status of truth. The point of depart is their localization in the crossing of two different historical movements: that of the medical illustrations, in its relation to the production of objective knowledge; and that of the researches about the localization, in the brain cortex, of complex behaviours and personality traits. Besides the establishment of some historical conditions of possibylity to the emergence of a cerebral neo-localizationism, this work pretends to stress some diferences in relation to preceding localizationist projects, and to emphasize the influence of the contemporary cultural context to the success e persuasive power of this kind of technologie.

abstract: Neuroimaging has appeared in the courtroom as a type of `evidence' to support claims about whether or not criminals should be held accountable for their crimes. Yet the ability to abstract notions of culpability and criminal behavior with confidence from these imagines is unclear. As there remains much to be discovered in the relationship between personal responsibility, criminal behavior, and neurological abnormalities, questions have been raised toward neuroimaging as an appropriate means to validate these claims. This project explores the limits and legitimacy of neuroimaging as a means of understanding behavior and culpability in determining appropriate criminal sentencing. It highlights key philosophical issues surrounding the ability to use neuroimaging to support this process, and proposes a method of ensuring their proper use. By engaging case studies and a thought experiment, this project illustrates the circumstances in which neuroimaging may assist in identifying particular characteristics relevant for criminal sentencing. I argue that it is not a question of whether or not neuroimaging itself holds validity in determining a criminals guilt or motives, but rather a proper application of the issue is to focus on the way in which information regarding these images is communicated from the `expert' scientists to the `non-expert' making decisions about the sentence that are most important. Those who are considering this information's relevance, a judge or jury, are typically not well versed in criminal neuroscience and interpreting the significance of different images. I advocate the way in which this information is communicated from the scientist-informer to the decision-maker parallels in importance to its actual meaning. As a solution, I engage Roger Pielke's model of honest brokering as a solution to ensure the appropriate use of neuroimaging in determining criminal responsibility and sentencing. A thought experiment follows to highlight the limits of science, engage philosophical repercussions, and illustrate honest brokering as a means of resolution. To achieve this, a hypothetical dialogue reminiscent of Kenneth Schaffner's `tools for talking' with behavioral geneticists and courtroom professionals will exemplify these ideas. / Dissertation/Thesis / Masters Thesis Biology 2014

abstract: Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for 70-90% of all TBI cases, yet its neuropathophysiology is still poorly understood. While a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (post-natal day 20) to repeat weight drop impact. Animals were anesthetized and subjected to sham or rmTBI once per day for 5 days. At 14 days post injury (PID), magnetic resonance imaging (MRI) revealed that rmTBI animals displayed marked cortical atrophy and ventriculomegaly. Specifically, the thickness of the cortex was reduced up to 46% beneath and the ventricles increased up to 970% beneath the impact zone. Immunostaining with the neuron specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker, 4-Aminophyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct "return to game" decision making in adolescents. / Dissertation/Thesis / Masters Thesis Biology 2014

Nos últimos anos, temos nos deparado com a difusão maciça e a popularização crescente de descrições biológicas para aspectos outrora pensados como mentais, sociais, ou relacionais. Visível em diversas arenas leigas e científicas, esta tendência freqüentemente elege o cérebro como o órgão privilegiado da sua atenção. A cada semana é divulgada uma nova localização cerebral correlacionada os mais variados aspectos comportamentais e ou de personalidade. Acompanhando este movimento, é notável o esforço intelectual e financeiro despendido nos últimos anos no campo da saúde mental, no sentido de fazer avançar pesquisas cujo foco central é a descoberta das bases neurobiológicas dos transtornos mentais. Esta tendência apontaria na direção de uma fusão entre a psiquiatria e a neurologia em uma disciplina única, de teor fisicalista, chamada por alguns de cerebrologia. Dentre os acontecimentos que serviram de alicerce para a legitimação e a popularização desta tendência, o desenvolvimento nas últimas décadas de novas técnicas e tecnologias de visualização médica, como a tomografia por emissão de pósitrons (PET scan) e a ressonância magnética funcional (fMRI), foi fundamental. Elas permitiram a construção de imagens das mais diversas categorias nosográficas construídas no campo psiquiátrico, veiculando tacitamente uma série de pressupostos e promessas. Malgrado o imaginário cultural sustentado por estas tecnologias e todo o esforço despendido nas últimas décadas no sentido de se tentar localizar os marcadores biológicos dos transtornos psiquiátricos, não há, até o presente momento, nenhum resultado conclusivo que autorize o diagnóstico por imagem de nosografias como a esquizofrenia, a depressão, e muito menos o jogo patológico. Apesar de todo o alarde midiático e dos montantes milionários direcionados para pesquisas nesta área, os resultados concretos obtidos até agora não estão livres das mais ferozes controvérsias. Entretanto, ainda que estejamos muito longe da construção de mapas precisos para as perturbações mentais é espantoso o poder de convencimento que as neuro-imagens comportam na atualidade. Os scans são exibidos como verdades visuais, ou fatos acerca das pessoas e do mundo, numa proporção muito superior aos dados que apresentam. Alguns críticos chamam este aspecto de neurorealismo, ou de retórica da auto-evidência. A intenção deste trabalho é problematizar o poder persuasivo que as neuro-imagens detém na contemporaneidade, especialmente quando utilizadas com a finalidade diagnóstica no campo da saúde mental. Se estas imagens transmitem uma ideia de neutralidade, transparência imediata e auto-evidência, este trabalho almeja inseri-las num contexto sócio-histórico, a partir do qual puderam adquirir sentido, familiaridade e valor de verdade. O ponto de partida é o de que elas estão localizadas no cruzamento de dois movimentos históricos distintos: o das ilustrações médicas, em sua relação com a produção de conhecimento objetivo; e o das pesquisas acerca da localização no córtex cerebral de comportamentos complexos e traços de personalidade. Além de estabelecer algumas condições históricas de possibilidade para a emergência de um neo-localizacionismo cerebral, mediado pelas novas tecnologias de imageamento, pretende-se enfatizar algumas descontinuidades com projetos anteriores e marcar a influência do contexto cultural da atualidade para o sucesso e poder persuasivo deste tipo de tecnologia. / Lately, we have seen the popularization and massive difusion of biological descriptions to aspects that we used to consider as social or mentaly based. Notable in scientific and lay environments, this tendency frequently chooses the brain as the privileged organ of its attention. Every week, a new cerebral locality, related to behavioral and personality traces, is publicized. Along with this movement, it is remarkable the intellectual and financial efforts undertaken in the last years in the domaine of mental health, to advance the researchs that aim to discover the neurobiological basis of the mental disorders. This tendency points to the fusion between psychiatry and neurology in only one discipline, phisicalistically based, sometimes called brainology. One of the most important events that served as a base to the legitimation and the popularization of this trend was the development, in the last decades, of the new medical imaging techniques and technologies, like the Positron Emission Tomography (PET scan) and the Functional Magnetical Ressonance Imaging (fMRI). These technologies allowed the image construction of almost every nosografic category made up in the psychiatric domaine, transmitting implicitly many assumptions and promises. Notwithstanding the cultural imaginary sustaned by these technologies and the efforts undertaken to localize the biological markers of psychiatric disorders, there isnt, until the present time, any conclusive result that entitle the imaging diagnostic of nosographies like schizophrenia, depression, and the pathogical gambling. In spite of the mediatic attention and the milionaires amounts destined to researchs in this field, the concret results obtained until now arent free from tough controversies. However, even considering we are very far from the construction of accurate maps for the mental disfunctions, its incredible the power of conviction that neuroimages have nowadays. The scans are exhibited as visuable truths, or facts concerning the people and the world, in a proportion much superior to the data they present. Some critics call such an aspect neurorealism, or rhetoric of auto-evidence. The aim of this work is to question the persuasive power acquired by the neuroimages nowadays, especially when addopted to diagnostic aims in the field of mental health. If these images pass the idea of neutrality, immediate transparence and auto-evidence, this work intends to include them in a social-historical context, through wich they have obtained meaning, familiarity, and the status of truth. The point of depart is their localization in the crossing of two different historical movements: that of the medical illustrations, in its relation to the production of objective knowledge; and that of the researches about the localization, in the brain cortex, of complex behaviours and personality traits. Besides the establishment of some historical conditions of possibylity to the emergence of a cerebral neo-localizationism, this work pretends to stress some diferences in relation to preceding localizationist projects, and to emphasize the influence of the contemporary cultural context to the success e persuasive power of this kind of technologie.

Apesar das evidências a favor da automaticidade no processamento de estímulos aversivos, especialmente na amígdala, a sua resposta parece ser dependente da disponibilidade de re- cursos atentivos. Dessa forma, a atenção pode atuar como um mecanismo de regulação emocional, importante para a compreensão de uma série de distúrbios psiquiátricos em que este mecanismo está prejudicado. Nesse estudo, investigamos o processo do regulação e- mocional pela atenção sob uma condição de grande demanda atentiva e com estímulos altamente aversivos. Imagens funcionais por ressonância magnética foram adquiridas de 22 voluntários saudáveis enquanto figuras emocionais (IAPS - International Afective Picture System), neutras e aversivas (corpos mutilados) eram apresentadas enquanto eles realiza- vam três tarefas diferentes, em que a atenção era manipulada. As imagens foram apresenta- das no centro do campo visual, enquanto apareciam duas barras, uma de cada lado da figu- ra. As três tarefas atentivas correspondiam a reconhecer: (1) a valência emocional da figura, (2) a semelhança na orientação das duas barras com diferenças de 0º ou 90º (tarefa fácil) e (3) a semelhança das mesmas com diferença de 0º ou apenas 6º (tarefa muito difícil). Nas análises de regiões de interesse (ROIs) observamos um padrão de regulação emocional, com dimuição da amplitude do sinal BOLD estimado, nas regiões da amígdala, ínsula ante- rior, cíngulo posterior e córtex pré-frontal medial, ventrolateral e orbitofrontal na tarefa fácil. Já na tarefa difícil, esse comportamento se manteve, com excessão do sinal da ínsula e do orbitofrontal, que voltou a subir, talvez, por um efeito de estresse. Verificamos uma maior amplitude do sinal BOLD na região dos córtices pré-frontal dorsolateral, parietal superior e área motora suplementar quando a atenção foi alocada para as tarefas de barras, supostamente, por um efeito da demanda maior de atenção. Nestes resultados, todo um conjunto de estruturas envolvidas no processamento emocional foi regulado pela manipu- lação da atenção nas tarefas. Também observamos uma correlação entre o traço de afeto positivo dos sujeitos e a estimativa do sinal BOLD da amígdala sob a regulação emocional. Estas evidências indicam que, mesmo para estímulos extremamente negativos, a disponibi- lidade de recursos de atenção e, talvez, mecanismos inibitório de controle cognitivos sobre a amígdala sejam fatores condicionantes da resposta emocional. / Because of the biological significance of motional stimuli, their processing is considered largely automatic. However, there are also evidences that processing of emotional stimuli requires some level of attention. Higher attention demands in a task may limit emotional processing which can be interpreted as an emotion regulation strategy. Our experiments utilized highly demanding attention task while also highly aversive and arousing visual stimuli comprising mutilated bodies is presented. The experiment employed a single task, which consisted of determining whether two peripheral bars were like oriented or not, such to evaluate further brain mechanisms involved in emotion regulation by functional mag- netic resonance imaging (fMRI). Our results revealed that task-irrelevant unpleasant images slowed reaction time during the performance of the main easy task, but not at highly de- manding one which is suggesting of emotion suppression. Such modulatory effect was also revealed by ROI analysis showing that many brain regions, including regions of amygdala, anterior insula, posterior cingulate, and medial, ventrolateral and orbitofrontal prefrontal cortex have their processing of emotional visual stimuli reduced by attentional manipula- tions while there were BOLD signal increases in dorsolateral prefrontal and superior parie- tal cortex respective to attention demand. These results suggest that attentional manipula- tions that more fully consume attentional resources in order to demonstrate that the proc- essing of emotional stimuli is limited.

Orientadores: Fernando Cendes, Li Li Min / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-10T05:20:09Z (GMT). No. of bitstreams: 1 Betting_LuizEduardoGomesGarcia_D.pdf: 9629246 bytes, checksum: a5717d51675609b6835960db129c8d3b (MD5) Previous issue date: 2006 / Resumo: Epilepsias generalizadas idiopáticas (EGI) constituem de 20-40% das epilepsias e de forma oposta às epilepsias parciais, anormalidades estruturais não são esperadas. De acordo com a idade de início e o tipo principal de crise, as EGI são divididas principalmente em epilepsia ausência infantil e juvenil (EA), epilepsia mioclônica juvenil (EMJ) e epilepsia com crises tônico-clônicas generalizadas (CTCG). Os limites entre estas subsíndromes são imprecisos e a classificação muitas vezes é difícil. Devido às características semelhantes, alguns autores consideram a EGI como uma única patologia com múltiplos fenótipos (continuum biológico). O eletroencefalograma (EEG) auxilia no diagnóstico das EGI especialmente quando evidencia descargas do tipo espícula onda-lenta generalizadas com atividade de base normal. Entretanto, o EEG pode ser normal e até mesmo mostrar focalidades dificultando o diagnóstico. A ressonância magnética (RM) não é realizada de forma rotineira em pacientes com EGI. Contudo, novas técnicas de aquisição e processamento de imagens vêm detectando anormalidades sutis nestes indivíduos. O objetivo deste estudo foi investigar a fisiopatologia das EGI através da análise de características clínicas, eletroencefalográficas e de neuroimagem. Inicialmente, as características dos EEGs de 180 pacientes com diagnóstico clínico de EGI foram avaliadas. 493 exames foram analisados. Em 33% dos pacientes o EEG inicial foi característico e em 22% o exame evidenciou focalidades. Após a identificação de focalidades utilizamos a neuroimagem convencional (análise visual) na avaliação de 134 pacientes com EGI. Observamos anormalidades na RM de 27 (20%) pacientes. A maioria das anormalidades não apresentou relação direta com as crises. Utilizamos a técnica da morfometria baseada em voxel (MBV) para investigar lesões discretas eventualmente não identificadas na neuroimagem de rotina. Esta técnica permite a comparação entre grupos de imagens aumentando a chance de detecção de anormalidades. Observamos aumento na concentração de substância cinzenta (CSC) localizada no córtex frontal de pacientes com EMJ (n=44) e EA (n=24). Observamos também uma maior CSC na região anterior do tálamo nos pacientes com crises de ausência (n=47). Avaliando as focalidades clínicas e de EEG de 22 pacientes com EGI utilizando a MBV, observamos áreas de aumento da CSC em 8 dos 9 (89%) pacientes com EMJ, 5 dos 6 (83%) pacientes com EA e 5 dos 7 (71%) pacientes com CTCG ao despertar. A volumetria do tálamo foi realizada para investigar o aumento de CSC sugerido pela MBV. A comparação entre 147 pacientes e um grupo controle evidenciou um maior volume da região anterior do tálamo nos pacientes com crises de ausência. Nossos resultados revelam que a fisiopatologia das EGI envolve o tálamo e o córtex cerebral. As diversas alterações na neuroimagem quantitativa apresentadas por cada subsíndrome sugerem um diferente mecanismo para as EGI. Este achado fortalece o conceito de diferentes doenças com fenótipos semelhantes. Mais do que isso, nossos achados indicam, uma alteração estrutural no cérebro destes indivíduos. Os diversos fenótipos estão relacionados a diferentes mecanismos fisiopatológicos. As focalidades observadas no EEG e na RM refletem a patogênese das crises em pacientes com EGI / Abstract: Idiopathic generalized epilepsies (IGE) represent 20-40% of all epilepsies and opposed to partial epilepsies, structural abnormalities are not expected. According to the age of onset and the main seizure type, IGE are divided mainly in childhood and juvenile absence epilepsy (AE), juvenile myoclonic epilepsy (JME) and generalized tonic-clonic seizures (GTCS). The limits between these subsyndromes are unclear and sometimes classification is difficult. Because of the similar characteristics, some authors consider IGE as a single pathology with multiple phenotypes (biological continuum). Electroencephalogram (EEG) helps the IGE diagnosis specially when it shows the generalized spike and wave discharges with normal background. However, the EEG may be normal or even disclose focalities difficulting the diagnosis. Magnetic resonance imaging (MRI) is not routinely performed in patients with IGE. In spite of this, new techniques of acquisition and processing of the images are detecting subtle abnormalities in these individuals. The objective of this study was to investigate the pathophysiology of the IGE using the clinical, EEG and neuroimaging features. Initially, the characteristics of the EEGs of 180 patients with clinical diagnosis of IGE were evaluated. 493 exams were analyzed. In 33% of the patients the initial EEG was characteristic and in 22% the exam revealed focalities. After the identification of the focalities, we used conventional neuroimaging (visual analysis) on the evaluation of 134 patients with IGE. We observed abnormalities in the MRI of 27 (20%) patients. Most of the abnormalities were not directly related to the seizures. We used the voxel base morphometry (VBM) technique to evaluate the images. This technique allows comparisons between groups of images increasing the chances of detecting abnormalities. We observed increased gray matter concentration (GMC) localized in the frontal cortex of patients with JME (n=44) and AE (n=24). We also observed increased GMC in the anterior thalamic region of patients with absence seizures (n=47). Evaluating the clinical and EEG focalities of 22 patients with IGE using VBM, we observed areas of increased GMC in 8 of 9 (89%) patients with JME, 5 of 6 (83%) patients with AE and 5 of 7 (71%) patients with GTCS on awakening. The volumetry of the thalamus was performed to investigate the increased GMC suggested by the VBM. The comparison between 147 patients with a control group showed increased volume of the anterior thalamic region in patients with absence seizures. Our results revealed that the pathophysiology of the IGE involves the thalamus and the cerebral cortex. The several abnormalities on the neuroimage presented by each subsyndrome suggest a different mechanism for the IGE. This finding strengths the concept of multiple diseases with similar phenotypes. Furthermore, our findings indicate a structural abnormality in the brain of these individuals. The several phenotypes are related with different pathophysiological mechanisms. The focalities present on the EEG and in the MRI reflect the pathogenesis of the seizures in patients with IGE / Doutorado / Neurociencias / Doutor em Fisiopatologia Medica