Human infants have been shown to have an innate capacity to acquire their mother tongue. In recent decades, the advent of the functional magnetic resonance imaging (fMRI) technique has made it feasible to explore the neural basis underlying language acquisition and processing in children, even in newborn infants (for reviews, see Kuhl & Rivera-Gaxiola, 2008; Kuhl, 2010) . Spontaneous low-frequency (< 0.1 Hz) fluctuations (LFFs) in the resting brain have been shown to be physiologically meaningful in the seminal study (Biswal et al., 1995) . Compared to task-based fMRI, resting-state fMRI (rs-fMRI) has some unique advantages in neuroimaging research, especially in obtaining data from pediatric and clinical populations. Moreover, it enables us to characterize the functional organization of the brain in a systematic manner in the absence of explicit tasks. Among brain systems, the language network has been well investigated by analyzing LFFs in the resting brain. This thesis attempts to investigate the functional connectivity within the language network in typically developing preschool children and the covariation of this connectivity with children’s language development by using the rs-fMRI technique. The first study (see Chapter 2.1; Xiao et al., 2016a) revealed connectivity differences in language-related regions between 5-year-olds and adults, and demonstrated distinct correlation patterns between functional connections within the language network and sentence comprehension performance in children. The results showed a left fronto-temporal connection for processing syntactically more complex sentences, suggesting that this connection is already in place at age 5 when it is needed for complex sentence comprehension, even though the whole functional network is still immature. In the second study (see Chapter 2.2; Xiao et al., 2016b), sentence comprehension performance and rs-fMRI data were obtained from a cohort of children at age 5 and a one-year follow-up. This study examined the changes in functional connectivity in the developing brain and their relation to the development of language abilities. The findings showed that the development of intrinsic functional connectivity in preschool children over the course of one year is clearly observable and individual differences in this development are related to the advancement in sentence comprehension ability with age. In summary, the present thesis provides new insights into the relationship between intrinsic functional connectivity in the brain and language processing, as well as between the changes in intrinsic functional connectivity and concurrent language development in preschool children. Moreover, it allows for a better understanding of the neural mechanisms underlying language processing and the advancement of language abilities in the developing brain.

Nous proposons un algorithme basé sur une approche orientée d'ensemble de système dynamique pour extraire une organisation grossière de l'espace d'état de cerveau sur la base des signaux de l'EEG. Nous l'utilisons pour comparer l'organisation de l'espace d'état des données simulées à grande échelle avec la dynamique cérébrale réelle au repos chez des sujets sains et pathologiques (SEP). / We propose an algorithme based on set oriented approach of dynamical system to extract a coarse grained organization of brain state space on the basis of EEG signals. We use it for comparing the organization of the state space of large scale simulation of brain dynamics with actual brain dynamics of resting activity in healthy and SEP subjects.

L'IRMf de repos qui repose sur l'étude des fluctuations du signal BOLD chez un sujet au repos, pourrait permettre d'explorer les mécanismes du handicap dans la Sclérose En Plaques (SEP). En utilisant l'IRMf de repos, ce travail a eu pour objectif de caractériser la réorganisation fonctionnelle des patients atteints de SEP et ses liens avec leur handicap.Nous avons d'abord réalisé une étude combinant IRMf de repos et d'activation au stade précoce de la SEP et montré l'existence d'une corrélation entre la plasticité fonctionnelle du système moteur des patients au repos et durant la tâche. Nous avons ensuite montré l'existence d'une augmentation diffuse du niveau de connectivité fonctionnelle des patients présentant une SEP débutante, corrélée à leurs performances. Dans la 3ème partie, nous avons objectivé l'existence d'un déclin dynamique de la topologie fonctionnelle corrélée à la progression du handicap grâce à une étude longitudinale utilisant la théorie des graphes. Enfin, nous avons démontré que le gain fonctionnel obtenu par la rééducation chez les patients SEP était corrélé à une augmentation de connectivité fonctionnelle du réseau cérébral par défaut et central exécutif et de densité de substance grise dans le cortex frontal.Nos travaux montrent l'existence d'une réorganisation cérébrale fonctionnelle complexe et dynamique dans la SEP qui pourrait correspondre à des phénomènes compensatoires, dont le déclin avec l'évolution de la maladie participe à la progression du handicap. Ils démontrent l'intérêt de l'IRMf de repos pour la compréhension des substrats anatomo-fonctionnels du handicap dans la SEP et comme potentiel instrument futur d'évaluation thérapeutique. / Resting-state fMRI (rs-fMRI) may provide important clue concerning disability in multiple sclerosis (MS) by exploring the spontaneous BOLD fluctuations at rest in the whole brain. The aim of this work is to depict the functional reorganization of resting-state networks in MS patients and to assess its potential relationships with disability.In the first part, we performed an fMRI protocol combining a rs-fMRI and task-associated fMRI during a motor task, in a group of early MS patients. This study evidenced a direct association between reorganization of connectivity at rest and during activation in the motor system of patients. In the second rs-fMRI study, we evidenced an increased of the global level of connectivity in most of the rs-networks, strongly associated with the level of disability of patients. In the third part, we evidenced in a 2-year longitudinal study using graph theoretical approach that MS patients exhibited a dynamical alteration of functional brain topology that significantly correlated with disability progression. In the last part, we evidenced that the transient clinical improvement following physical rehabilitation in MS patients is associated with reversible plasticity mechanisms located in the default mode network, the central executive network and in the left fronto-orbital cortex. These works evidence that MS patients exhibit a complex and dynamical functional reorganization of rs-networks, significantly associated with disability progression. This PhD thesis confirms that rs-fMRI is a relevant biomarker of pathophysiology leading to disability in MS and represents a promising tool for therapeutic assessment of MS patients in the future.

Avaliar acuradamente o gasto energético de repouso (GER) é de extrema importância no suporte nutricional e a análise de composição corporal influencia seu valor. O estudo teve como objetivos desenvolver equações preditivas de GER por meio de dados de composição corporal obtidos por exame de bioimpedância eléctrica multifrequencial por espectroscopia (BIS); avaliar a adequação das fórmulas mais usuais de predição do GER; medir a correlação dos parâmetros gerados por BIS com o GER, analisar a concordância e a correlação dos dados gerados pelos aparelhos de bioimpedância de frequência simples (BIA) e BIS, além da concordância entre os métodos de classificação do estado nutricional por Índice de Massa Corporal (IMC) e por %MG (Porcentual de Massa Gorda) avaliada por BIA e BIS. Caracterizou-se como um estudo transversal observacional desenvolvido com brasileiros saudáveis, ambos os sexos, entre 20 e 40 anos de idade, estratificados em subgrupos pelo IMC (subnutrido, n=40; eutrófico, n=120; com sobrepeso, n=118 e com obesidade, n=114) e pelo %MG (baixa gordura, n=17; gordura adequada, n=101; excesso de gordura, n=91 e obesidade, n=183). O GER foi medido por calorimetria indireta (CI). Houve emprego do teste de correlação de Spearman e de Pearson e do gráfico de dispersão para avaliar as associações entre as variáveis e de modelos de regressão linear múltipla no desenvolvimento das equações, por método Stepwise. Aplicou-se o teste de BlandAltman, o coeficiente de correlação intraclasse, o teste de Wilcoxon e o coeficiente de correlação kappa para análise de concordância entre medidas e classificações e o teste de Mann-Whitney e Kruskal-Wallis para comparação entre os subgrupos (p<0,05). O GER predito foi considerado adequado quando se encontrou entre 90 e 110% do GER medido por CI. Desenvolveu-se uma equação para a amostra total por sexo e uma para cada categoria do IMC e do %MG e as mesmas apresentaram baixos valores de coeficientes de determinação (R2). As maiores correlações entre as variáveis independentes com o GER ocorreram para o peso, IMC, Massa Gorda7 (MG) e Massa de Tecido Adiposo. Todas as equações usuais avaliadas não foram capazes de predizer corretamente o GER em metade da amostra. As classificações do estado nutricional realizadas por meio do IMC e %MGBIA obtiveram concordância fraca com aquela por %MGBIS. A concordância entre BIA e BIS foi baixa: tecidos corporais de maior hidratação foram superestimados e os menos hidratados subestimados, por BIA frente a BIS, e os vieses entre os dois equipamentos foram maiores com o aumento do IMC. Assim, as equações desenvolvidas apresentaram baixo R2, impossibilitando sua aplicação no cenário clínico. Já as equações de predição do GER avaliadas exibiram baixa adequação, não se recomendando seu uso. A classificação do estado nutricional por meio do IMC subestima as quantidades de MG, sendo mais adequada a utilização de composição corporal para caracterização nutricional. BIA e BIS geram resultados distintos: o tamanho corporal aparece como um fator de confusão na distinção das massas corporais analisadas, mas, a distribuição e a quantidade de água corporal total apresentam-se como fatores limitantes de maior força / The accurate assessment of resting energy expenditure (REE) is extremely important in nutritional support for energy supply adjustment and body composition analysis plays a significant role in determining its value. The objectives of this thesis was to develop prediction equations of REE using body composition assessment data by bioelectrical impedance; assess the adequacy of the more usual prediction equations of REE against the measured value; measuring the correlation of the parameters generated by multifrequency spectroscopy bioelectrical impedance (BIS) in GER and analyze the agreement and correlation of data generated by bioelectrical impedance devices of simple frequency (BIA) and (BIS), in total sample and between subgroups stratified by body mass index (BMI) and body fat percentage (%BF), in addition to assess the agreement between the classification of nutritional state by BMI and %BF generated by BIA and BIS . This was an observational cross-sectional study with healthy Brazilians, both sexes, between 20 and 40 years old, stratified into subgroups by BMI (malnourished, n=40; eutrophic, n=120; overweight, n=118 and obese, n=114) and by %BF (low fat, n=17; suitable fat, n=101; excess fat, n=91 and obesity, n=183). There was the use of anthropometric and epidemiological parameters and those generated by BIS analysis in the equations\'s development. REE was measured by indirect calorimetry (IC). Employment Spearman correlation test and scatterplot to assess the associations between the variables and multiple linear regression models in the development of the equations. Application of Bland-Altman analysis, intraclass correlation coefficient, Wilcoxon test and kappa correlation coefficient for agreement analysis between measurements and classifications and the Mann-Whitney and Kruskal-Wallis test to compare the subgroups (p <0,05). Thus, an equation was developed for the total female sample and one for each of the last three categories of BMI and% BF, the same for males. The equations obtain low values of determination coefficient (R2). The highest correlations between the independent variables with REE occurred, for both females and males, with weight, BMI, BF and9 Adipose Tissue Mass. All the usual equations evaluated had low accuracy since none was able to correctly predict GER in 50% or more of the sample, either for the whole sample or stratified by BMI and %BF. The equations with the highest percentages of the sample within the adequacy limits were Owens, Henry-Rees and Livingston-Kohlstadt 2. The worst percentages of the sample within the adequacy limits were those of Ireton-Jones, FAO/WHO/UN 2 and Frankenfield 1. The nutritional status rankings performed through BMI and %BFBIA obtained weak agreement with that by %BFBIS, tending to classify the individual one or two levels below, underestimating the presence of %BF. The agreement between BIA and BIS was low since the equipment presented different results for all the variables, either in the total sample or in the stratified subgroups. The BIA against BIS underestimated the amounts related to the BF and total body water variables and overestimated those concerning the FFM and BCM. The biases between the two equipments were greater with the increase of BMI. Thus, the developed equations have low R2, which makes it impossible to apply them in the clinical setting. The most common and predictive GER prediction equations presented low accuracy, not proving to be adequate for use in clinical practice. The classification of nutritional status through BMI results in errors that compromise the approach of nutritional therapy, underestimating the amounts of BF and its deleterious potencies, so it is more appropriate to evaluate it through body composition. BIA and BIS generate different results, and body size appears as a confounding factor in the body mass distinction analyzed by BIA, but the distribution and amount of total body water is a limiting factor of greater strength for the BIA

Obesity is a growing problem globally. Currently 2.3 billion adults are overweight, and this number is rising. The most common method for weight loss is calorie counting, in which to lose weight a person should be in a calorie deficit. Basal Metabolic Rate accounts for the majority of calories a person burns in a day and it is therefore a major contributor to accurate calorie counting. This paper uses a Dynamic Bayesian Network to estimate Basal Metabolic Rate (BMR) for a sample of 219 individuals from all Body Mass Index (BMI) categories. The data was collected through the Lifesum app. A comparison of the estimated BMR values was made with the commonly used Harris Benedict equation, finding that food journaling is a sufficient method to estimate BMR. Next day weight prediction was also computed based on the estimated BMR. The results stated that the Harris Benedict equation produced more accurate predictions than the metabolic model proposed, therefore more work is necessary to find a model that accurately estimates BMR.

Neozygites floridana is an important natural enemy of Tetranychus urticae in many crops, including strawberry. In this crop there has been some changes in the production system from open field to low tunnel. This new system presents benefits to strawberry production, moreover this system increases problems with spider mites and some fungal plant pathogens; consequently increasing the use of pesticides. In order to integrate N. floridana in the management of spider mites in strawberry there are still many important aspects to be revealed on the biology, epizootiology of the fungus and the effect of crop systems on its prevalence in the field. For this, three studies were performed, being the first one about the effect of strawberry production systems (low tunnel and open field) and pesticide application on population dynamics of two-spotted spider mite T. urticae, its natural enemies (N. floridana and predatory mites), and plant diseases, the experiment was performed in Inconfidentes-MG. The population of T. urticae attained the highest level in treatments with chemical control of pest, independently of the crop system, low tunnel or open field. The fungus N. floridana was observed late in both crop seasons, in treatments with and without inoculative releases, and has suggested that it might be a natural occurrence of the fungus. The highest prevalence of the fungus were observed in treatments with high densities of T. urticae. The predatory mites occurred naturally during the two crop seasons, and the most abundant species was Neoseiulus anonymus (Chant) (57.5%). The incidence of fungal plant diseases are greater in the open field than in low tunnel, however it seems that the crop system do not affect the new disease \"vermelhao\". The second study aimed to reveal the abiotic and biotic factors involved in the regulation of resting spores formation in the hosts T. urticae and T. evansi. The Brazilian isolate ESALQ1420 produced a large number of resting spores (51.5%) in T. urticae at a temperature 11 °C, photoperiod of 10L:14D, light intensity of 42-46 (?mol m-2s-1), on non-senescent plants. Small percentages of mites with resting spores (0-5 %) were found for the Norwegian isolate NCRI271/04 under the conditions tested, and very low percentages of resting spores (up to 1%) were observed in T. evansi infected by the Brazilian isolate ESALQ1421.The third study was therefore conducted phylogenetic analysis of isolates of N. floridana and develops efficient real-time PCR-based analysis for detection and quantification of N. floridana propagules from the soil. The phylogenic three showed that Neozygites is a fungal group far from other Entomophthoromycota and that N. floridana present high intra-specific variability. This data indicates that the isolates from different Tetranychus species may be in fact different Neozygites species, not described yet. We developed a real-time PCR probe for detection and quantification of N. floridana in the soil. This molecular probe was successful in quantifying N. floridana at relatively high DNA concentrations seeded into the soil. / Neozygites floridana é um importante inimigo natural de Tetranychus urticae em diversas culturas, incluindo morango. Nesta cultura tem havido uma mudança no sistema de produção, passando de cultivo em campo aberto para túnel baixo. Este novo sistema apresenta benefícios na produção de morango, no entanto pode aumentar problemas com ácaros fitófagos e algumas doenças fúngicas, consequentemente aumentando o uso de agrotóxicos. Para a integração de N. floridana no manejo de ácaros fitófagos em morango, existem ainda muitos aspectos importantes a serem conhecidos sobre a biologia, epizootiologia do fungo e efeito dos sistemas de cultivo sobre a sua prevalência em campo. Para isso três estudos foram realizados, sendo o primeiro estudo sobre o efeito de sistemas de produção de morango (túnel baixo e campo aberto) e da aplicação de agrotóxicos sobre a dinâmica populacional do acaro rajado T. urticae, seus inimigos naturais (N. floridana e ácaros predadores) e doenças de plantas, o experimento foi realizado em Inconfidentes-MG. A população de T. urticae atingiu altos níveis em tratamentos com controle químico de pragas, independente do sistema de cultivo, túnel baixo ou campo aberto. O fungo N. floridana foi observado no final de ambos os ciclos de cultivos, nos tratamentos com e sem liberações inoculativas, sugerindo que houve incidência natural do fungo. As maiores prevalências do fungo foram observadas em tratamentos com altas densidades de T. urticae. Os ácaros predadores ocorreram naturalmente durante os dois ciclos de cultivo, sendo Neoseiulus anonymus (Chant) a espécie mais abundante (57.51%). A incidência de doenças fúngicas foi maior em campo aberto do que em túnel baixo, no entanto parece que o sistema de cultivo não afetou a incidência da nova doença vermelhão. No segundo estudo objetivou-se conhecer os fatores abióticos e bióticos envolvidos na formação de esporos de resistência nos hospedeiros T. urticae e Tetranychus evansi. O isolado brasileiro ESALQ1420 produziu um grande número de esporos de resistência (51.5%) em T. urticae, a uma temperatura de 11 ° C, fotoperíodo de 10F:14E, intensidade de luz de 42-46 (?mol m-2s-1), em plantas senescentes. Pequenas percentagens de ácaros com esporos de resistência (0-5%) foram encontrados para o isolado Norueguês NCRI271/04 sob as condições testadas, e muito baixas percentagens de esporos de resistência (ate 1%) foram observados em T. evansi infectados pelo isolado brasileiro ESALQ1421. O terceiro estudo objetivou analisar filogeneticamente os isolados de Neozygites patogênicos a ácaros, e desenvolver ferramenta utilizando PCR em tempo real para a detecção e quantificação de propágulos de N. floridana a partir do solo. A arvore filogenética mostrou que Neozygites e um grupo de fungos distante dos demais Entomophthoromycota, e que estes fungos apresentaram alta variabilidade intraespecífica entre isolados de N. floridana. Estes resultados indicam que isolados provenientes de diferentes espécies hospedeiras do gênero Tetranychus podem ser de fato diferentes espécies de Neozygites não descritas ainda. Desenvolveu-se uma sonda molecular para detecção e quantificação de N. floridana no solo utilizando PCR em tempo real. Esta sonda foi eficiente na quantificação de N. floridana, em concentrações relativamente altas de DNA inoculado no solo.

Propósito: Observar obesas pré e pós-dieta hipocalórica moderada, mais treinamento em circuito ou caminhada. quanto a variáveis nutricionais. Métodos: Grupos: treinamento em circuito, CIRC, n = 26, índice de massa corporal (IMC, kg/m2) = 33,2 ± 7,9 (Média±desvio padrão); idade = 32,6 ± 9,7 anos; e treinamento em caminhada, CAM, n = 24, IMC = 29,2±3,4; idade = 38,8 ± 10,5 anos. Avaliações: a composição corporal, coleta de urina e sangue, calorimetria indireta e testes físicos eram obtidos no inicio (M1) e final (M2) do estudo. Treinamento: mês 1 = 1 h x 3 d/semana; e mês 2 = 1 h x 4 d/semana. Dieta: foi adaptada do registro alimentar de uma semana, ajustado ao gasto energético de repouso (GER) e balanceada, com a seguinte proporção: 20% de proteínas; 20% de gorduras; e 60% de carbohidratos. Resultados: Pré-intervenção: 76% tinham algum familiar obeso; havia sintomatologia indicativa de: 60% ansiosas, 12% depressivas, 34% compulsivas e 32% distúrbio do sono, avaliadas por questionário no exame clínico. Foram encontrados níveis alterados de colesterol total (CT, mg/dL), e ou frações em 22% das sujeitas. O peso, IMC, o índice abdômem/quadril (IAQ), a soma de oito pregas cutâneas (SP8) se correlacionaram significativamente a quatro variáveis bioquímicas, e a circunferência do abdômen (CAb), e o percentual de gordura por antropometria (%GAntro) a cinco. Intervenção: O peso, IMC, %GAntro, endomorfia, massa gorda por bioimpedância (MGBia) e percentual de gordura por bioimpedância (%GBia), foram reduzidos significativamente nos dois grupos. O CIRC melhorou significativamente em todos (seis) e o CAM em três testes físicos. O CIRC teve significância para: ¯glicose (Gli), ¯AU, ¯CT, ¯Tg (todos em mg/dL), ­glóbulos vermelhos (GV) (mm3) e ­hematócrito (Ht) (%); e o CAM para: ¯Gli, ¯AU, ¯HDL, ­CT/HDL, ­GV, ­Ht. O GER não teve diferença em ambos os grupos. Conclusões: Pré-intervenção: Os dados antropometricos indicam boa correlação com os fatores bioquímicos de risco, mas não tem uma tendência constante. A taxa CT/HDL apresentou correlação com todas as medidas antropométircas e a Gli com nenhuma. A obesidade destas mulheres parece ter múltiplos fatores e o estilo de vida papel determinante. Intervenção: A atividade física per se foi importante para causar modificações nutricionais e da composição corporal nestas obesas. O CIRC teve melhor associação com o incremento da performance física e dados bioquímicos sanguineos e ambos os grupos preservaram o GER. / Purpose: To observe obese women before and after a low-calorie diet plus circuit training or jogging regarding nutritional parameters. Methods: Groups: circuit training, CIRC, n = 26, body mass index (BMI, kg/m2) = 33.2 ± 7.9 (Mean±SD), age = 32.6 ± 9.7 years; and jogging training, JOGG, n = 24, BMI = 29.2 ± 3.4; age = 38.8 ± 10.5 years. Evaluations: body composition, collection of urine and blood samples, indirect calorimetry and physical tests were performed at the beginning (M1) and at the end (M2) of the study. Training: month one: 1 h x 3 d/week; month two: 1 h x 4 d/week. Diet: was adapted on the basis of a one week feeding record feed and adjusted to the resting metabolic rate (RMR) measured by indirect calorimetry, with the following proportion: 20% protein, 20% fat; and 60% carbohydrate. Results: Pre-intervention: 76% had one or more obese family members; there were symptoms indicating that 60% were anxious, 12% depressive, 34% compulsive, and 32% had sleep disorders, evaluated by a questionnaire during clinical examination. Altered levels of total cholesterol (TC) and/or fractions were found in 22% of the subjects. Weight (W), BMI, waist/hip ratio (WHR), and the sum of eight skin folds (8SF), were significantly correlated with four biochemistry variables, and abdominal circumference (AbC), and anthropometric fat percentage (%FAnthro) were correlated with five. Intervention: Weight, BMI, %FAnthro, endomorphy, body fat mass by bioimpedance (BFMBia) and percent body fat by bioimpedance (%FBia) were reduced in both groups. CIRC significantly increased performance in all (six) tests and the JOGG in three physical tests. CIRC showed significant differences for: ¯glucose (Glu), ¯UA, ¯TC (TC), ¯Tg (all in mg/dL), ­red blood cells (RBC) (mm3) and ­hematocrit (Ht) (%); and JOGG for: ¯Glu, ¯UA, ¯HDL, ­CT/HDL, ­RBC, ­Ht. The RMR was not significantly reduced in both groups. Conclusions: Pre-intervention: Anthropometric data indicated a good correlation with biochemical factors, but did not show a constant tendency. CT/HDL showed correlation with all anthropometric measurements and Glu with none. The obesity of these women appears to have multiple factors, with life style playing a determinant role. Intervention: Physical activities were determined to favor body composition, reduced weight and blood markers. CIRC were better in terms of physical performance and blood markers. Both types of training were sufficient to prevent a fall of RMR.

A presença de redes cerebrais funcionais ativadas durante o repouso é bem conhecida e verificada por diferentes técnicas de imagens, como as Imagens por Ressonância Magnética funcionais (IRMf) baseadas no contraste dependente do nível de oxigenação do sangue (BOLD, Blood Oxygenation Level Dependent). Entretanto, apesar de ser atualmente o método não invasivo convencional para tais estudos, o contraste BOLD é sensível a diferentes parâmetros hemodinâmicos (fluxo sanguíneo cerebral, CBF; volume sanguíneo cerebral e extração de oxigênio), cuja relação não é completamente conhecida em diversas patologias. Por outro lado, o método de Marcação dos Spins Arteriais (ASL) é uma técnica de IRM não invasiva que fornece mapas quantitativos de CBF e pode ser usada para avaliar as redes de repouso. Portanto, o objetivo do presente estudo foi investigar a viabilidade de usar sequências de ASL (pulsada e pseudocontínua), disponíveis para o uso na rotina clínica, para o estudo da conectividade funcional do cérebro em estado de repouso. Imagens de ASL e BOLD, de 23 indivíduos jovens e saudáveis, foram adquiridas em um equipamento de 3T. Após o pré-processamento usual das imagens e cálculos dos mapas de perfusão, CBF e pseudo-BOLD (pBOLD), a partir das imagens de ASL, as redes cerebrais de repouso foram obtidas pela Análise de Componentes Independentes (ICA) e pelo método baseado em semente. Utilizando ICA, a análise em grupo conjunta de pBOLD e BOLD identificou cinco redes: rede de modo padrão (DMN), visual, auditiva, saliência e motora. Quando analisados separadamente, os dados de pBOLD mostraram apenas as redes DMN e visual, enquanto os dados de BOLD mostraram também as redes auditiva, saliência, motora, atentiva e frontoparietais direita e esquerda. Para ambas as análises, comparações entre as redes de pBOLD e BOLD apresentaram similaridades de moderadas a altas. Entretanto, nenhuma rede foi observada utilizando os dados de perfusão e CBF. Já as análises baseadas em sementes mostraram correlações significativas, para as séries temporais de pBOLD e CBF, entre regiões que constituem algumas redes de repouso conhecidas (DMN, visual, sensorial-motora, atentiva e frontoparietal). Os valores obtidos para a força das conectividades nas redes de pBOLD e CBF se correlacionaram com aqueles obtidos nas redes de BOLD. As diferenças no desempenho de ASL e BOLD devem-se a uma combinação de fatores, como relação sinal ruído e resolução temporal. Além disso, a natureza dos sinais não é a mesma. O sinal BOLD é influenciado por diferentes parâmetros fisiológicos e é proveniente principalmente de grandes veias; enquanto o sinal de ASL é proveniente da rede de capilares, fornecendo especificidade espacial mais alta para a atividade neuronal, além de permitir a quantificação do CBF, que está relacionado mais diretamente ao metabolismo cerebral. Portanto, o presente estudo mostrou ser possível investigar a conectividade funcional do cérebro no estado de repouso com uma sequência comercial, apesar das limitações técnicas da ASL. Além disso, as séries temporais de CBF e BOLD refletem diferentes aspectos do cérebro em repouso, fornecendo informações complementares dos seus processos fisiológicos / The presence of functional brain networks activated during resting state is well known and has been verified by different imaging techniques, such as the functional Magnetic Resonance Imaging (fMRI) based on the Blood Oxygenation Level-Dependent (BOLD) contrast. Although BOLD-fMRI is currently the conventional non invasive method for such studies, BOLD contrast is sensitive to different hemodynamic parameters (Cerebral Blood Flow, CBF; cerebral blood volume and oxygen extraction fraction), whose relationship is not fully understood in several pathologies. In contrast, the Arterial Spin Labeling (ASL) MRI technique is a non invasive tool for CBF quantification and can be used to investigate resting-state networks. Therefore, the goal of the present study was to investigate the feasibility of using ASL sequences (pulsed and pseudocontinuous), available for clinical routine use, for the study of functional connectivity of the brain at rest. ASL and BOLD images of 23 healthy young subjects were acquired in a 3T machine. After the usual image pre-processing and quantification of perfusion, CBF and pseudo-BOLD (pBOLD) maps, from ASL images, resting-state brain networks were obtained by Independent Component Analysis (ICA) and a seed-based method. Five networks were identified in a joint analysis of pBOLD and BOLD: Default Mode Network (DMN), visual, auditory, salience, and motor. When analyzed separately, pBOLD showed only the DMN and visual networks, while BOLD also showed auditory, salience, motor, attentive, right and left frontoparietal networks. For both analyses, comparisons between pBOLD and BOLD networks showed from moderate to high similarities. However, no network was obtained from perfusion and CBF time series. Seed-based analysis showed significant correlations, for pBOLD e CBF time series, between regions that integrate some known networks (DMN, visual, sensorial-motor, attentive and frontoparietal). Functional connectivity strength obtained from pBOLD and CBF networks correlated with the ones from BOLD data. Differences in performance with ASL and BOLD are due to a combination of factors, such as SNR and temporal resolution. Moreover, the nature of the signals is not the same. BOLD signal is influenced by different physiologic parameters and comes mainly from large veins; while ASL signal comes from small capillaries, providing higher spatial specificity regarding neural activity, in addition to allow the quantification of CBF, which is closer related to the cerebral metabolism. In conclusion, the present study showed the feasibility of investigating functional connectivity of the brain at rest using a commercial ASL sequence, even with its technical limitations. Moreover, CBF and BOLD time series reflect different aspects of the resting-state brain and provide complementary information on its physiological processes

Les objectifs de cette thèse étaient de caractériser les corrélats neuronaux fonctionnels et structurels de l'abolition de la conscience observés pendant le coma et d'identifier les signatures neuronales précoces de la récupération neurologique à partir de cet état. Pour atteindre ce but, nous avons étudié des patients cérébrolésés, recrutés au stade aigu du coma, à l'aide de l'IRM fonctionnelle au repos et IRM structurale. Nos résultats indiquent une réorganisation topologique globale du cerveau des patients, reflétée par une dédifférenciation et une réduction de la résilience des réseaux fonctionnels au repos d'ordre élevé. Ces anomalies sont accompagnées d'une perte de connexions fronto-pariétales à longue distance. Au niveau régional, nous avons observé un schéma complexe de diminution et d'augmentation de la densité de connexion fonctionnelle entre le cortex postéromédial et le cortex préfrontal médial : régions précédemment décrites pour avoir un rôle critique dans la conscience. De manière intéressante, ces modifications de densité de connexion étaient significativement liées à la récupération des patients trois mois après le coma. Enfin, l'analyse multimodale a permis de démontrer une association significative entre la connectivité fonctionnelle et l'intégrité structurelle cérébrales antéro-postérieure, fournissant des informations importantes sur le lien structure/fonction au décours de ces troubles acquis de la conscience. / The aim of the present thesis was to characterize the functional and structural neural correlates of acute consciousness abolition induced by severe brain injury and identify early neural signatures of long-term neurological recovery. To do so, we studied brain-injured patients, recruited in the acute stage of coma, using resting-state functional and structural MRI. Our findings indicated a global topological brain reorganization in coma patients, reflected in dedifferentiated and less resilient high-order resting-state functional networks, paralleled with a loss of long-range fronto-parietal connections. On a regional level, we found a complex pattern of voxel-wise decrease and increase in functional connection density between the posteromedial cortex and the medial prefrontal cortex, regions previously described to have a critical role in conscious processing. These connection density patterns seemed to permit outcome prediction in patients, assessed three months post-coma. Furthermore, the multi-modal MRI analysis demonstrated a significant association between antero-posterior functional connectivity and structural integrity, providing further insights into the pathological underpinning of conscious processing.

Extracting structure from initially incomprehensible streams of events is fundamental to a range of human abilities: from navigating in a new environment to learning a language. These skills rely on our ability to extract spatial and temporal regularities, often with minimal explicit feedback, that is known as statistical learning. Despite the importance of statistical learning for making perceptual decisions, we know surprisingly little about the brain circuits and how they change when learning temporal regularities. In my thesis, I combine behavioural measurements, Diffusion Tensor Imaging (DTI) and resting-state fMRI (rs-fMRI) to investigate the structural and functional circuits that are involved in statistical learning of temporal structures. In particular, I compare structural connectivity as measured by DTI and functional connectivity as measured by rs-fMRI before vs. after training to investigate learning-dependent changes in human brain pathways. Further, I combine the two imaging modalities using graph theory and regression analyses to identify key predictors of individual learning performance. Using a prediction task in the context of sequence learning without explicit feedback, I demonstrate that individuals adapt to the environment’s statistics as they change over time from simple repetition to probabilistic combinations. Importantly, I show that learning of temporal structures relates to decision strategy that varies among individuals between two prototypical distributions: matching the exact sequence statistics or selecting the most probable outcome in a given context (i.e. maximising). Further, combining DTI and rs-fMRI, I show that learning-dependent plasticity in dissociable cortico-striatal circuits relates to decision strategy. In particular, matching relates to connectivity between visual cortex, hippocampus and caudate, while maximisation relates to connectivity between frontal and motor cortices and striatum. These findings have potential translational applications, as alternate brain routes may be re-trained to support learning ability when specific pathways (e.g. memory-related circuits) are compromised by age or disease.