Objetivo: avaliar as diferenças estruturais e funcionais entre o cérebro de pacientes com tontura postural-perceptual persistente (TPPP) e controles. Método: o estudo foi aprovado pela comissão de ética local. As voluntárias deram consentimento formal. 16 mulheres com TPPP (44.7±8.3 anos) e 16 controles (46.5±8.5 anos) foram pareadas por sexo e idade. Imagens de ressonância magnética funcional (RMf) e estrutural foram adquiridas utilizando sistema 3.0 T durante a visibilização de figuras padronizadas do International Affective Pictures System (IAPS) com valência negativa, positiva e neutra. Realizou-se análise estrutural segmentar e volumétrica com o programa Freesurfer e funcional com o FSL (FMRIB Software Library) usando correção fatia-tempo e de movimento, suavização espacial (5mm FWHM), e normalização no espaço standard MNI (Montreal Neurological Institute). O modelo linear geral (GLM) incluiu regressores por grupo e condições. Adotou-se um limiar de Z = 3.09 (p < 0.001) para cada vóxel, e um nível de significância para correção de clusters de p < 0.05. O Z=2.3 foi utilizado na comparação entre grupos. Resultados: o grupo com TPPP apresentou ativação na região do córtex cingulado anterior na diferença entre contrastes positivos e negativos por queda de sinal na visibilização de estímulos negativos; enquanto o grupo controle teve efeito BOLD (Blood Oxygen Level Dependent) positivo na região amigdaliana bilateralmente na diferença entre contrastes negativos e positivos. Houve ativação em giro angular esquerdo na diferença entre contrastes negativos e positivos e entre grupos (pacientes > controles). Conclusão: ativação em região amigdaliana em resposta a estímulos negativos em relação aos positivos é frequentemente encontrada em pacientes com ansiedade e síndrome do estresse pós-traumático, mas não foi vista no nosso grupo com TPPP, só no controle. Por outro lado, o grupo com TPPP mostrou desativação da região do córtex cingulado anterior, um modelo descrito em algumas, mas não em todas as disfunções ansiosas, e não identificado no grupo controle. Além disto, o efeito BOLD positivo na região do giro angular esquerdo, área não inclusa no sistema límbico, com múltiplas funções, dentre elas a orientação espacial, indicam que mais trabalhos são necessários para elucidar o mecanismo cerebral da TPPP / Objectives: evaluate structural and functional differences in brain among patients with postural perceptual persistent dizziness (PPPD) and controls. Method: The study was approved by local IRB, and volunteers gave their informed consent. Sixteen women with PPPD (44.7 ± 8.3 years-old) were compared to 16 controls (46.5 ± 8.5 years-old) matched by age and gender. Structural and functional brain images were acquired in a 3.0T MRI system while subjects were presented with pictures from a standard reference (International Affective Pictures System - IAPS) with positive, neutral and negative emotional valence stimuli. Structural images were analysed in Freesurfer program and fMRI images in FSL (FMRIB Software Library) using slice-time and motion correction, spatial smoothing (5mm FWHM), and normalized images into MNI standard space. The GLM model included regressors for groups and conditions. A threshold Z-score = 3.09 (p < 0.001) was used for each voxel, and was adopted the correction by clusters at a p < 0.05 significance level. A Z-score = 2.3 was used for comparison between groups. Results: the PPPD group showed increased brain response at anterior cingulate cortex when comparing [positive > negative] stimuli as a result of deactivation during negative stimuli, whereas the control group had positive BOLD when comparing [negative > positive] stimuli at amigdala region in both sides. PPPD group had increased brain response when comparing [negative>positive] stimuli and [patients > controls] in the left angular gyrus. Conclusion: The amygdala region activation in control group in response to negative than positive stimuli is a pattern often found in patients with anxiety and traumatic stress but not was seen in our patient group. In contrast, they showed deactivation of the anterior cingulate cortex in response to negative stimuli, a pattern found in some, but not all anxiety disorders, and not identified in the control group. Otherwise, the positive BOLD in angular gyrus, brain area not included in limbic system, with multiple functions, including spatial orientation, indicate that more work is needed to elucidate brain mechanisms underlying PPPD

Objetivo: avaliar as diferenças estruturais e funcionais entre o cérebro de pacientes com tontura postural-perceptual persistente (TPPP) e controles. Método: o estudo foi aprovado pela comissão de ética local. As voluntárias deram consentimento formal. 16 mulheres com TPPP (44.7±8.3 anos) e 16 controles (46.5±8.5 anos) foram pareadas por sexo e idade. Imagens de ressonância magnética funcional (RMf) e estrutural foram adquiridas utilizando sistema 3.0 T durante a visibilização de figuras padronizadas do International Affective Pictures System (IAPS) com valência negativa, positiva e neutra. Realizou-se análise estrutural segmentar e volumétrica com o programa Freesurfer e funcional com o FSL (FMRIB Software Library) usando correção fatia-tempo e de movimento, suavização espacial (5mm FWHM), e normalização no espaço standard MNI (Montreal Neurological Institute). O modelo linear geral (GLM) incluiu regressores por grupo e condições. Adotou-se um limiar de Z = 3.09 (p < 0.001) para cada vóxel, e um nível de significância para correção de clusters de p < 0.05. O Z=2.3 foi utilizado na comparação entre grupos. Resultados: o grupo com TPPP apresentou ativação na região do córtex cingulado anterior na diferença entre contrastes positivos e negativos por queda de sinal na visibilização de estímulos negativos; enquanto o grupo controle teve efeito BOLD (Blood Oxygen Level Dependent) positivo na região amigdaliana bilateralmente na diferença entre contrastes negativos e positivos. Houve ativação em giro angular esquerdo na diferença entre contrastes negativos e positivos e entre grupos (pacientes > controles). Conclusão: ativação em região amigdaliana em resposta a estímulos negativos em relação aos positivos é frequentemente encontrada em pacientes com ansiedade e síndrome do estresse pós-traumático, mas não foi vista no nosso grupo com TPPP, só no controle. Por outro lado, o grupo com TPPP mostrou desativação da região do córtex cingulado anterior, um modelo descrito em algumas, mas não em todas as disfunções ansiosas, e não identificado no grupo controle. Além disto, o efeito BOLD positivo na região do giro angular esquerdo, área não inclusa no sistema límbico, com múltiplas funções, dentre elas a orientação espacial, indicam que mais trabalhos são necessários para elucidar o mecanismo cerebral da TPPP / Objectives: evaluate structural and functional differences in brain among patients with postural perceptual persistent dizziness (PPPD) and controls. Method: The study was approved by local IRB, and volunteers gave their informed consent. Sixteen women with PPPD (44.7 ± 8.3 years-old) were compared to 16 controls (46.5 ± 8.5 years-old) matched by age and gender. Structural and functional brain images were acquired in a 3.0T MRI system while subjects were presented with pictures from a standard reference (International Affective Pictures System - IAPS) with positive, neutral and negative emotional valence stimuli. Structural images were analysed in Freesurfer program and fMRI images in FSL (FMRIB Software Library) using slice-time and motion correction, spatial smoothing (5mm FWHM), and normalized images into MNI standard space. The GLM model included regressors for groups and conditions. A threshold Z-score = 3.09 (p < 0.001) was used for each voxel, and was adopted the correction by clusters at a p < 0.05 significance level. A Z-score = 2.3 was used for comparison between groups. Results: the PPPD group showed increased brain response at anterior cingulate cortex when comparing [positive > negative] stimuli as a result of deactivation during negative stimuli, whereas the control group had positive BOLD when comparing [negative > positive] stimuli at amigdala region in both sides. PPPD group had increased brain response when comparing [negative>positive] stimuli and [patients > controls] in the left angular gyrus. Conclusion: The amygdala region activation in control group in response to negative than positive stimuli is a pattern often found in patients with anxiety and traumatic stress but not was seen in our patient group. In contrast, they showed deactivation of the anterior cingulate cortex in response to negative stimuli, a pattern found in some, but not all anxiety disorders, and not identified in the control group. Otherwise, the positive BOLD in angular gyrus, brain area not included in limbic system, with multiple functions, including spatial orientation, indicate that more work is needed to elucidate brain mechanisms underlying PPPD

<p>The central theme of the present thesis revolves around the exploration of similarities and differences in brain activity patterns invoked by the component processes underlying mnemonic, executive and attentional functions. The primary aim was to identify and functionally characterize commonly recruited brain regions in terms of shared component processes, which has been a largely neglected area of research in cognitive neuroscience. The vast majority of functional brain imaging investigations of cognition has focused on delineating differences between cognitive functions or processes, with the purpose of isolating the unique functional neuroanatomy that underlies specific cognitive domains. By contrast, the present thesis builds on the results from three imaging studies that focused primarily on detecting commonalities in functional brain activity across different forms of memory processes. In study I, the imaging data from two positron emission tomography (PET) experiments were re-analyzed to identify common activation patterns associated with nine different memory tasks incorporated across the experiments, three each separately indexing working memory, episodic memory, and semantic memory. A generic prefrontal cortex (PFC) network involving discrete subregions of the left hemisphere located in ventrolateral (BA 45/47), dorsolateral (BA 9/44/46), and frontopolar (BA 10) sectors of PFC, as well as a midline portion of the frontal lobes, encompassing the dorsal part of the anterior cingulate cortex (ACC) (BA 24/32), was conjointly recruited across all tasks. In study II, we used a novel mixed blocked/event-related functional magnetic resonance imaging (fMRI) design, which enables separation of brain responses associated with different temporal dynamics to further investigate commonalities of neural activation across working memory, episodic memory, semantic memory, and attention/vigilance. A similar set of common PFC regions, as that discovered in Study I, was found to elicit overlapping brain activity across all memory tasks, with a subset of regions also activated in the attention/vigilance task. Furthermore, the task-induced brain activity was dissociated in terms of the temporal profiles of the evoked neural responses. A common pattern of sustained activity seen across all memory tasks and the attention task involved bilateral (predominantly right-lateralized) ventrolateral PFC (BA 45/47), and the dorsal ACC (BA 24/32), which was assumed to reflect general processes of attention/vigilance. A pattern of sustained activity elicited in all memory tasks, in the absence of attention-related activity, involved the right frontopolar cortex (BA 10), which was assumed to reflect control processes underlying task set maintenance. In addition, common transient activation evoked in the memory tasks relative to the attention task was found in the dorsolateral (BA 9/44) and ventrolateral (BA 47) PFC, the superior parietal cortex (BA 7), and cerebellum. In study III, a mixed fMRI design was used to assess the degree of common brain activity associated with increased executive demand, which was independently manipulated within episodic and working memory. Unitary control modulations involved a shared tonic executive component subserved by fronto-striatal-cerebellar circuitry, assumed to govern top-down context processing throughout task periods, and a stimulus-synchronous phasic component mediated by the intraparietal sulcus (BA 7), assumed to support dynamic shifting of the ‘focus of attention’ among internal representations. Collectively, the theoretical implications of shared neural mechanisms are discussed, with a special focus on human memory and its multifaceted relationships with attention and executive control functions. Finally, the presented imaging data are used to outline a tentative hierarchical neurocognitive model that attempts to give an account of how different unitary component processes might work together during cognitive task performance.</p>

The central theme of the present thesis revolves around the exploration of similarities and differences in brain activity patterns invoked by the component processes underlying mnemonic, executive and attentional functions. The primary aim was to identify and functionally characterize commonly recruited brain regions in terms of shared component processes, which has been a largely neglected area of research in cognitive neuroscience. The vast majority of functional brain imaging investigations of cognition has focused on delineating differences between cognitive functions or processes, with the purpose of isolating the unique functional neuroanatomy that underlies specific cognitive domains. By contrast, the present thesis builds on the results from three imaging studies that focused primarily on detecting commonalities in functional brain activity across different forms of memory processes. In study I, the imaging data from two positron emission tomography (PET) experiments were re-analyzed to identify common activation patterns associated with nine different memory tasks incorporated across the experiments, three each separately indexing working memory, episodic memory, and semantic memory. A generic prefrontal cortex (PFC) network involving discrete subregions of the left hemisphere located in ventrolateral (BA 45/47), dorsolateral (BA 9/44/46), and frontopolar (BA 10) sectors of PFC, as well as a midline portion of the frontal lobes, encompassing the dorsal part of the anterior cingulate cortex (ACC) (BA 24/32), was conjointly recruited across all tasks. In study II, we used a novel mixed blocked/event-related functional magnetic resonance imaging (fMRI) design, which enables separation of brain responses associated with different temporal dynamics to further investigate commonalities of neural activation across working memory, episodic memory, semantic memory, and attention/vigilance. A similar set of common PFC regions, as that discovered in Study I, was found to elicit overlapping brain activity across all memory tasks, with a subset of regions also activated in the attention/vigilance task. Furthermore, the task-induced brain activity was dissociated in terms of the temporal profiles of the evoked neural responses. A common pattern of sustained activity seen across all memory tasks and the attention task involved bilateral (predominantly right-lateralized) ventrolateral PFC (BA 45/47), and the dorsal ACC (BA 24/32), which was assumed to reflect general processes of attention/vigilance. A pattern of sustained activity elicited in all memory tasks, in the absence of attention-related activity, involved the right frontopolar cortex (BA 10), which was assumed to reflect control processes underlying task set maintenance. In addition, common transient activation evoked in the memory tasks relative to the attention task was found in the dorsolateral (BA 9/44) and ventrolateral (BA 47) PFC, the superior parietal cortex (BA 7), and cerebellum. In study III, a mixed fMRI design was used to assess the degree of common brain activity associated with increased executive demand, which was independently manipulated within episodic and working memory. Unitary control modulations involved a shared tonic executive component subserved by fronto-striatal-cerebellar circuitry, assumed to govern top-down context processing throughout task periods, and a stimulus-synchronous phasic component mediated by the intraparietal sulcus (BA 7), assumed to support dynamic shifting of the ‘focus of attention’ among internal representations. Collectively, the theoretical implications of shared neural mechanisms are discussed, with a special focus on human memory and its multifaceted relationships with attention and executive control functions. Finally, the presented imaging data are used to outline a tentative hierarchical neurocognitive model that attempts to give an account of how different unitary component processes might work together during cognitive task performance.

L’objectif de cette thèse a été de comprendre les mécanismes cérébraux associés aux symptômes du trouble de stress post-traumatique (TSPT), ainsi que les mécanismes cérébraux modulés par la disparition des symptômes, en utilisant la thérapie de désensibilisation et de retraitement de l’information par les mouvements oculaires (Thérapie EMDR). Cette thérapie associe rappel du traumatisme et stimulations bilatérales alternées (SBA). Premièrement, en utilisant l’IRM fonctionnelle (IRMf), nous avons mis en évidence une altération de l’activité fonctionnelle du système de récompense dans le TSPT, correspondant à une mobilisation déséquilibrée des processus motivationnels cognitifs et hédoniques (étude 1). Deuxièmement, par l’intermédiaire d’une étude en IRMf au repos, nous avons montré que les patients présentent des altérations de connectivité fonctionnelle entre un réseau neuronal impliqué dans les processus mnésiques et émotionnels, et un réseau neuronal impliqué dans les processus attentionnels (étude 2). Troisièmement, nous avons montré que les structures initialement altérées par la pathologie évoluent après rémission symptomatique, suggérant un rétablissement des altérations neuronales induites par le stress chronique (étude 3). Enfin, nous avons montré que les SBA employées dans la thérapie EMDR facilitent l’extinction de la peur ainsi que la récupération de cette extinction au sein d’un groupe de volontaires sains (étude 4). Ainsi, ces travaux offrent de nouvelles perspectives en termes de modélisation de la pathologie, et offre de nouvelles pistes de réflexion quant à la prise en charge thérapeutique de ce trouble. / Posttraumatic Stress Disorder (PTSD) is a debilitating psychiatric disorder that arises in the aftermath of a traumatic event. To date, the Eye Movement Desensitization and Reprocessing therapy (EMDR) therapy has shown to be the most efficient therapy for the treatment of PTSD. The aim of this thesis was therefore to understand neural mechanisms underlying PTSD and its recovery. To do so, we conducted four studies. In a first study, we showed alterations in the reward circuit activity in PTSD patients, which may underlie an imbalance mobilization of cognitive and hedonic motivational processes, possibly contributing to emotional numbing in PTSD (study 1). Following this, an altered resting state functional connectivity between a network associated with attentional processes and another associated with emotional and memory processes was also found, suggesting an atypical emotional regulation and attention processing (study 2). A third study showed changes of grey matter density in regions involved in emotional regulation after symptoms remission by EMDR therapy. Finally, we were also able to replicate, in PTSD patients, the fear extinction and fear extinction recall facilitation by bilateral alternating stimulations (BAS) a major component of EMDR therapy, previously demonstrated in animal studies. Taken together, the present findings of these studies contribute to enlarge our knowledge, opening new ways of thinking the actual model of explaining the PTSD. More importantly, we believe that our findings may contribute to improve therapeutic strategies to significantly ameliorate the life of these patients.

Orientador: Roberto Jose Maria Covolan / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin / Made available in DSpace on 2018-08-12T12:47:40Z (GMT). No. of bitstreams: 1 Mesquita_RicksonCoelho_D.pdf: 22300712 bytes, checksum: 11bd3fc16a125afc1c2cd8b4d18bc2e2 (MD5) Previous issue date: 2009 / Resumo: A atividade neuronal relacionada a um determinado estímulo ou tarefa induz uma cadeia de complexos eventos biológicos no cérebro. O aumento no consumo de energia induz um acréscimo na demanda por glicose e oxigênio no tecido extravascular. Fatores bioquímicos e neuronais induzem variações nos vasos sanguíneos que resultam em alterações de uxo sanguíneo, volume e oxigenação. Embora extensivamente investigada, esta cascata de eventos ainda é pouco compreendida. Neste projeto, procuramos descrever o acoplamento entre os níveis celular, metabólico e vascular associado à ativação funcional do cérebro. Usando medidas eletro fisiológicas, modelamos os sistemas neuro-vascular e neuro-metabólico para descrever a hemodinâmica cerebral medida através de técnicas ópticas. Resultados obtidos em ratos durante a estimulação de um fio de bigode mostraram que a determinação de uma função resposta para cada sistema, assumido como linear, descreve bem o comportamento hemodinâmico e possibilita o estudo dos estados vascular e metabólico caracterizados pelos parâmetros medidos. A partir de experimentos multimodais de NIRS e fMRI, desenvolvemos metodologias inovadoras para a determinação de imagens metabólicas, capazes de prever variações do consumo de oxigênio com boa resolução espacial e temporal. Por fim, analisamos a in u^encia de parâmetros fisiológicos no sinal óptico, mostrando a contribuição importante da pressão sanguínea na composição deste. Medidas de correlação temporal foram projetadas para gerar mapas de correlação vascular que podem ser aplicados ao estudo da conectividade vascular cerebral, tanto em indivíduos normais como em pacientes com patologias cerebrais. / Abstract: Task-associated neuronal activity leads to a complex chain of biological events within the brain. The increased energetics gives rise to elevated glucose and oxygen consumption in the tissue. Biochemical and neuronal factors induce changes in blood vessels and variations in blood ow, volume and oxygenation. Although it has been extensively investigated, this cascade of events is still poorly understood and highly debated. In this project, the aim was to describe the coupling among the cellular, metabolic and vascular levels associated to functional brain activation. Using electrophysiological measurements, we modeled the neuro-vascular and neuro-metabolic systems in order to describe cerebral hemodynamics as seen through optical techniques. Results obtained in rats during whisker-barrel stimulation showed that the determination of a response function for each system, assumed as linear, can describe the hemodynamic behavior and allow the study of the vascular and metabolic states characterized by the measurements. From multimodal experiments of NIRS and fMRI, we developed unique methods to the determination of metabolic images, which can predict changes in oxygen consumption with good temporal and spatial resolution. Finally, we analyzed the in uence of the physiology in the optical signal, and showed the importance of taking into account blood pressure oscillations into this signal. Measurements of temporal correlation were projected to generate vascular correlation maps that may be useful to the study of cerebral vascular connectivity, both in normal subjects and in patients with cerebral pathologies. / Doutorado / Metodos Oticos de Analise / Doutor em Ciências

Le vieillissement cérébral normal est caractérisé par un déclin progressif de la capacité de traitement des informations en particulier dans le système de la mémoire de travail. Il apparaît donc essentiel d'explorer l'organisation corticale cérébrale sous-jacente au mécanisme de la mémoire de travail dont l'évaluation est rendu possible par l'imagerie par résonance magnétique fonctionnelle (IRMf). Les objectifs de notre travail ont consisté à identifier, dans une large cohorte d'individus âgés en bonne santé, les réorganisations des réseaux neuronaux en relation avec (i) l'augmentation de la difficulté d'une tâche de mémoire de travail, (ii) l'âge des individus au cours de la tâche et (iii) la performance de la tâche pendant un état de repos. Trois cent quatre-vingt participants âgés (82 ans, 56% femmes) issus de la cohorte des Trois Cités de Montpellier ont été sélectionnés pour réaliser un examen d'IRMf comprenant une tâche de DIR (reconnaissance d'item en élément différé) et un état de repos. La tâche de DIR s'organisait en trois phases : (i) présentation – une, trois ou six lettres – (ii) rétention – écran blanc – et (iii) réponse – après la présentation d'une lettre cible, le participant indique si cette lettre cible faisait partie ou non de l'ensemble de départ. Dans une première partie, après avoir localisé les régions activées lors des trois phases de la tâche, nos analyses de covariance ont pu identifier, simultanément à la difficulté croissante de la tâche, une augmentation de l'activation dans les réseaux du central exécutif et de saillance pendant les trois phases de la tâche ainsi qu'une diminution dans le réseau du mode par défaut pendant la phase de stimulation et dans les régions limbiques et des ganglions de la base pendant la phase de rétention. Ces résultats suggèrent une interaction entre les réseaux d'augmentation et de diminution. Dans une deuxième partie, nous avons exploré l'effet de l'âge sur l'augmentation de l'activité simultanément avec la difficulté croissante de la tâche. Pendant la phase de stimulation, une réduction de l'activation dans le lobule pariétal gauche a été identifiée chez les individus très âgés par rapport aux individus âgés jeunes suggérant la mise en jeu d'un décalage antéro-postérieur lorsque l'âge augmente. Dans une troisième partie, les réseaux impliqués dans la mémoire de travail (central exécutif, saillance et mode par défaut) ont été mis en évidence pendant l'état de repos. Notre travail a montré que la connectivité fonctionnelle et la performance sont corrélées par : (i) une réduction au sein des réseaux de saillance et du mode par défaut suggérant une altération des processus mémoriels et attentionnels et (ii) une augmentation au sein du réseau du central exécutif évoquant l'implication d'un processus compensatoire. L'ensemble de ces résultats indiquent la présence de réorganisations cérébrales des réseaux neuronaux (saillance, central exécutif et mode par défaut) sous-tendant la mémoire de travail au cours du vieillissement cérébral normal. / Normal brain aging is characterized by a progressive decline in information processing ability in particular in the system of working memory. Therefore, it is essential to examine neural substrates underlying the working memory system which can be assessed by functional magnetic resonance imaging (fMRI). The aim of our work is to explore, in a large cohort of healthy elderly individuals, reorganizations in the networks in relation to (i) increase task load during a DIR (delayed item recognition) task, (ii) age during increase DIR task load and (iii) the performance in the DIR task during a resting state. Three hundred and eighty elderly participants (82 years, 56% women) from the Three-City cohort in Montpellier have been selected to perform an fMRI exam including a DIR task and a resting state. DIR task consisted of three phases: (i) stimulation – presentation of one, three or six letters - (ii) retention - blank screen to hold the stimulus items in mind - and (iii) probe - after the presentation of a target letter, the participant indicates whether or not this probe matched a letter in the study array. In the first work, using a covariance analysis, we observed, when the difficulty of the DIR task increases, simultaneously increased activation in salience and central executive networks during three phases separately of the DIR task and decreased activation in DMN during stimulation phase and in limbic regions and deep grey nuclei during retention phase. It may be hypothesized that salience and central executive networks interact in a complex way with DMN and limbic regions and deep grey nuclei. In the second work, age effects on load-dependent increases activations of the task were explored. Reduced activation in the left parietal lobe was identified in very old individuals compared to young old individuals during the stimulation phase suggesting an involvement of posterior–anterior shift with increasing age. In the third work, networks implicated in working memory (central executive, salience and the default mode networks) were highlighted by independent component analysis during the resting state. Our findings have confirmed that the functional connectivity and performance are related by: (i) a decreased in the both salience and the default mode networks and (ii) an increased in the central executive network. We can suggest that the decreased functional connectivity within the salience and the default mode networks could be due attentional and memory processes alterations and/or altered motivation. The increased functional connectivity within the central executive network could be related to compensatory mechanisms meanwhile elders would perform more poorly. All of these studies indicate that brain reorganizations of neural networks (salience, central executive and default mode) underlying working memory in normal brain aging.

Obsessive-compulsive disorder (OCD) is heterogeneous. Clinical presentation of OCD differs by sex and age-of-onset and evidence supports classification based on these subtypes. The prevalence of OCD in the general population is 2%. However, it has been established that women tend to experience onset and exacerbation of OCD during reproductive milestones. In particular, the prevalence of postpartum OCD is between 4 to 9%. This study seeks to examine the effects of past childhood maltreatment and S/Lg-allele status of the 5-HTTLPR polymorphism on perinatal obsessive-compulsive symptoms and aberrant resting state functional connectivity in the postpartum period. Forty women participated in the first visit and sixteen women have been followed up with in the postpartum period. 5-HTTLPR genotype was determined from whole blood samples via polymerase chain reaction and a restriction fragment length digest. We used the Yale-Brown Obsessive-Compulsive Scale and Perinatal Obsessive-Compulsive scale to measure symptom severity. Resting state functional connectivity was determined from functional magnetic resonance imaging data. Obsessive-compulsive symptoms during late pregnancy are significantly predicted by 5-HTTLPR genotype, past history of total childhood maltreatment or childhood emotional neglect and trait anxiety symptoms. Whereas obsessive-compulsive symptoms during the postpartum period are predicted by poor sleep quality and childhood emotional maltreatment or 5-HTTLPR genotype, childhood emotional maltreatment and trait anxiety symptoms. Seed to region-of-interest analysis was employed to evaluate resting state functional connectivity differences between OCD patients and healthy controls in the postpartum period. Compared to healthy controls, OCD patients show greater connectivity between the caudate nucleus with the orbitofrontal cortex, the pars triangularis and the cingulate area. The insular cortex shows decreased connectivity between the right and left, the dorsal anterior cingulate area and the pars opercularis. The amygdala has increased connectivity with the cingulate area, the calcarine fissure, the supramarginal gyrus and decreased connectivity with the gyrus rectus. The above clinical and neuroimaging findings are in line with past work. However, this is the first study to show both 5-HTTLPR genotype and history of childhood maltreatment predict obsessive-compulsive symptoms in a perinatal population. Further, the resting state data replicates findings in the OCD literature but the study is the first to show this in postpartum women. This study serves as a platform for future work to further investigate both gene-environment interactions and distinct neuroimaging correlates in perinatal OCD. / Thesis / Master of Science (MSc)

A lombalgia mecânica comum (LMC) representa um problema particularmente importante no ambiente ocupacional, muitas vezes associado a incapacidade, afastamento do trabalho e alto custo socioeconômico. O surgimento da neuroimagem funcional permitiu novos conhecimentos sobre a estrutura cerebral e a fisiologia da dor crônica. Embora os aspectos relacionados ao trabalho sejam importantes fatores de risco para a cronicidade, existem poucos estudos que abordam especificamente a fisiopatologia da LMC em indivíduos afastados do trabalho. A esse respeito, questionamos se um fator como a atenção, conhecida como um importante modulador da dor, poderia desempenhar um papel distintivo na modulação da dor nos indivíduos com LMC afastados do trabalho. Objetivos: comparar os correlatos neuronais entre indivíduos com lombalgia mecânica comum com afastamento do trabalho, com indivíduos lombálgicos sem afastamento. Métodos: Foram selecionados 74 indivíduos com LMC crônica, divididos em três grupos: indivíduos com LMC e afastamento do trabalho (LMC/A); indivíduos com LMC sem afastamento do trabalho (LMC) e indivíduos sem qualquer tipo de dor crônica e sem afastamento do trabalho (Controle). O estudo foi realizado no Hospital Israelita Albert Einstein (HIAE). A ressonância magnética funcional (RMf) foi utilizada durante o desempenho de dois paradigmas (dor e atenção). Resultados: Após a estimulação dolorosa, na comparação entre os grupos, verificamos diferença significativa na condição estimulação > repouso, sendo que o contraste LMC > LMC/A mostrou maior resposta hemodinâmica (efeito BOLD) no córtex cingulado anterior e giro frontal superior e médio direito (p < 0,001). No contraste controles > LMC/A, o grupo controle apresentou maior efeito BOLD em região do polo frontal e paracingulado (p = 0,002). Conclusão: Nosso estudo corrobora o conceito de que a presença de dor crônica está associada a uma alteração na plasticidade neuronal em áreas cerebrais que se estendem além das regiões somatossensoriais, para incluir áreas que processam emoções / Chronic low back pain (CLBP) is a particularly important problem in the occupational environment, often associated with incapacity, sick leave and high socioeconomic cost. The emergence of functional neuroimaging allowed new insights into the brain structure and physiology of chronic pain. Although work-related aspects are important risk factors for chronicity, there are few studies that specifically address the pathophysiology of CLBP in individuals with sick leave. In this regard, we questioned whether a factor such as the attention known as an important pain modulator could play a distinctive role in modulating pain in individuals with CLBP with sick leave. Objective The overall objective of this study is to compare the neuronal correlates between groups of individuals CLBP with or without sick leave. Methods We selected 74 individuals, divided into three groups: individuals with CLBP, functional incapacity and sick leave (CLBP_L); individuals with CLBP, functional disability without sick leave (CLBP_NL); individuals without any form of chronic pain and without sick leave (Control). Functional magnetic resonance imaging (fMRI) was used during the performance of two paradigms (pain and attention).Results After painful stimulation, a significant difference was observed in the stimulation > rest condition, while the CLBP > CLBP_L contrast showed a higher hemodynamic response in the anterior cingulate cortex and the right medium /superior frontal gyrus (p < 0.001) and in contrast controls > CLBP_L, the control group presented higher hemodynamic response in the frontal pole and paracingulate region (p = 0.002).Conclusions Our study corroborates the idea that the presence of chronic pain is associated with an alteration in neuronal plasticity involving brain areas linked to emotions and not just somatosensory areas

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