La hernie est une maladie racinaire affectant les Brassica, causée par Plasmodiophora brassicae. Le déploiement de variétés présentant des facteurs génétiques de résistances est le moyen de lutte principal contre cette maladie. Toutefois, l’efficacité de ces variétés résistantes dans les nouveaux systèmes d’agriculture durable, à bas intrant azoté, est encore à évaluer. Dans ce contexte, les questions de recherche posées dans cette thèse sont les suivantes : i) La modulation de la résistance à la hernie par la réduction de l’apport azoté est-elle génotype/isolat dépendante ? ii) Y-a-t-il un effet de la réduction des apports azotés sur l’architecture génétique de la résistance à la hernie chez le colza ? iii) Quels sont les réponses transcriptomiques et métabolomiques impliquées dans la réduction du développement des symptômes en condition de carence azotée ? Le criblage de la réponse de nombreux génotypes de colza vis-à-vis de plusieurs isolats de P. brassicae a été réalisé dans deux conditions de fertilisation azotée (8 mM et 1 mM de nitrate). Basé sur ces expériences, le contrôle génétique du développement des symptômes et de la production des spores de repos lors de l’infection par deux isolats (eH et K92-16) a été étudié par génétique de liaison chez une population biparentale et par génétique d’association chez un panel de colza d’hiver. Enfin, les réponses moléculaires impliquées dans la réduction du développement des symptômes observée chez le génotype ‘Yudal’ en condition 1mM ont été étudiées par des méthodes de RNA-seq et de métabolomique. L’impact de la fertilisation azotée sur la quantité de symptômes et la production de spores de repos est variable selon la combinaison génotype/isolat. Les modulations observées entraînent une augmentation de la résistance en condition 1mM. La fertilisation azotée module également l’effet (R2) de certains des Quantitative Trait Loci (QTL) impliqués dans la résistance. Dans le cas de l’isolat eH, elle affecte principalement l’effet des QTL C09 et C02. L’augmentation de résistance observée chez le génotype ‘Yudal’ en condition 1mM, vis-à-vis de l’isolat eH, semble liée à la surexpression de gènes impliqués dans l’assimilation des nitrates (famille NRT2) et dans le transport de l’auxine. / Clubroot is a Brassica root disease caused by Plasmodiophora brassicae. The use of varieties including genetic resistance factors is the most efficient strategy to manage clubroot disease. However, efficiency of these resistant varieties newly integrated in low-input agricultural systems (especially low nitrogen input) needs to be evaluated. In this context, the research questions investigated in this thesis are: i) Is clubroot resistance modulation by nitrogen fertilization genotype/isolate dependent? ii) Is there an effect of nitrogen fertilization reduction on the genetic architecture of clubroot resistance in rapeseed? iii) What are the transcriptomic and metabolomic responses implicated in symptom reduction under low nitrogen fertilization? To answer these questions, clubroot responses of several rapeseed genotypes were screened using different P. brassicae isolates under two nitrogen fertilizations (8mM and 1mM of nitrate). Based on this experiment, genetic control of symptom development and resting spore production during inoculation using two isolates (eH and K92-16) was studied by linkage analyses using a bi-parental population and by genome wide association using a winter rapeseed diversity set. Last, molecular responses implicated in symptom development, observed in ‘Yudal’ genotype under 1mM condition, were studied using RNA-seq and metabolomic methods. We revealed that impact of nitrogen fertilization on symptom quantity and resting spore production are dependent to genotype/isolate combination. Modulations observed were characterized by an increase of resistance under 1mM condition. Additionally, nitrogen fertilization modulates also the effect (R²) of some Quantitative Trait Loci implicated in clubroot resistance (QTL). Using eH isolate, nitrogen fertilization principally impacts C09 QTL and C02 QTL effects. Ultimately, increase of resistance observed on ‘Yudal’ genotype under 1mM condition, using eH isolate, seems to be related with overexpression of genes implicated in nitrate assimilation (NRT2 family) and auxin transport.

Orientador: Maria Rita Marques de Oliveira / Banca: Maria Rita Marques de Oliveira / Banca: Maria Jacira Silva Simões / Banca: Rozangela Verlengia / Resumo: A obesidade é uma doença estreitamente relacionada ao desenvolvimento da síndrome metabólica (SM) e é fundamentalmente um problema de balanço energético que se desenvolve quando a ingestão de energia proveniente dos alimentos é maior que o gasto energético total. O gasto energético total compreende a taxa metabólica de repouso, o efeito térmico dos alimentos e os gastos com atividade física e pode ser medido pela calorimetria indireta. O objetivo deste trabalho foi estudar a relação da taxa metabólica de repouso (TMR) em mulheres obesas com os componentes da SM e fatores relacionados. O grupo de estudo foi constituído por 35 mulheres com idade entre 18 e 40 anos, que apresentavam um índice de massa corporal (IMC) maior ou igual a 30 kg/m². Foram excluídas as mulheres portadoras de diabetes mellitus, hipotireoidismo, gestantes, lactantes e aquelas em tratamento (medicamentoso ou não) para obesidade e dislipidemias, além das portadoras de doenças graves. Foram aplicados um questionário para obtenção de dados sócio-demográficos, três recordatórios de 24 horas em dias não consecutivos sendo um final de semana e três diários de atividade física, aplicados no mesmo dia dos recordatórios. O comportamento alimentar foi avaliado pela escala de compulsão alimentar periódica (ECAP). Dentre as variáveis antropométricas foram avaliadas peso, estatura, circunferência de cintura, quadril e braço. A composição corporal (percentual de gordura e massa magra) foi avaliada pela bioimpedância elétrica e a TMR foi avaliada por meio do analisador de gases VO2000 MedGraphicsÒ. Foram ainda dosados em sangue o colesterol total e frações, glicose, insulina, proteína C reativa e triglicérides. As mulheres foram agrupadas quanto à presença ou não de SM e em tercil de TMR ajustada para a massa corporal (TMR/MC)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: It is known that obesity, a disease closely related to the development of the metabolic syndrome (MS), is basically a problem of energy balance and develops when energy intake exceeds total energy expenditure. Total energetic expenditure includes basal metabolic rate, the thermogenic effect of food and expenditures with physical activity and can be determined by indirect calorimetry. The objective of this study was to relate the basal metabolic rate (BMR) of obese women with MS components and related factors. The studied group included 35 women aged 18 to 40 years with a body mass index equal to or above 30 kg/m². Women with diabetes mellitus, hypothyroidism, severe diseases, women being treated for obesity and dyslipidemias and pregnant and lactating women were excluded from this study. A questionnaire to obtain sociodemographic data, three 24-hour dietary recalls in non-consecutive days one being during the weekend and three physical activity diaries administered on the same day as the 24-hour recalls were administered. Eating behavior was assessed by the binge eating scale (BES). The following anthropometric variables were assessed: weight, height and waist, hip and arm circumferences. Body composition (percentage of fat and lean mass) was determined by electrical bioimpedance and the basal metabolic rate was assessed by the gas exchange testing system MedGraphics VO2000®. The women were divided into groups with and without the MS and in BMR terciles adjusted for body mass (BMR/BM). The results showed that there was no significantly statistical difference between the groups with and without the MS regarding income, physical activity, presence of binge eating disorder, dietary macronutrient and micronutrient composition, energy intake, BMR, respiratory quotient (RQ), BMR/BM or MBR/LM. When the women were divided into BMR/BM terciles, BMR/BM was not associated with MS components... (Complete abstract click electronic access below) / Mestre

O presente trabalho avaliou a mortalidade de suínos no pré-abate através de análises anatomopatológica a fim de identificar as causas envolvidas. O estudo foi realizado durante os períodos de verão e inverno do ano de 2015 em um frigorífico do estado do Rio Grande do Sul que conta com Serviço de Inspeção Federal e está localizado na região do Vale do Taquari. No verão, foram contabilizadas 141 mortes do total de 117.260 (0,12%), enquanto que, no inverno, foram 75 mortes do total de 127.286 (0,05%). Dos 216 suínos mortos nos dois períodos, 170 foram submetidos a necropsia. Amostras foram examinadas no laboratório do Setor de Patologia Veterinária da Faculdade de Veterinária da Universidade Federal do Rio Grande do Sul. Entre as causas de morte diagnosticadas, as úlceras gástricas na região do quadrilátero esofágico e piloro foram as mais frequentes, sendo 29,2% (31/106) no verão e 32,8% (21/64) no inverno. As alterações pulmonares, como pneumonia enzoótica, influenza, broncopneumonia bacteriana e pleurite, foram o segundo diagnóstico mais frequente, sendo observado 15,1% (16/106) no verão e 18,8% (12/64) no inverno. A insuficiência cardíaca, incluindo pericardite bacteriana, endocardite bacteriana, cardiomiopatia hipertrófica, miocardite, infarto do miocárdio e neoplasia, apresentou-se em uma frequência de 14,2% (15/106) no verão e 9,4% (6/64) no inverno. A dilatação gástrica aguda causada pelo excesso de ração no estômago também foi um importante diagnóstico obtido, sendo 8,5% (9/106) no verão e 4,7% (3/64) no inverno. Rupturas de fígado foram observadas em 5,7% das mortes (6/106) no verão e 7,8% (5/64) no inverno, enquanto que rupturas de baço foram observadas em 0,9% das mortes (1/106) no verão e 1,6% (1/64) no inverno, representando diagnósticos importantes, mas pouco descritos na literatura como causa de morte. A enteropatia proliferativa foi diagnosticada em 5,7% dos casos (6/106) no verão e 4,7% (3/64) no inverno. A torção de mesentério foi responsável por 3,8% (4/106) das mortes ocorridas no verão e 6,2% (4/64) no inverno. Em menor frequência observaram-se as polisserosites, presente em 2,8% (3/106) dos suínos mortos no verão e 3,1% (2/64) no inverno. Já a fratura de fêmur somente foi observada em 0,9% dos casos (1/106) no período de verão. Casos inconclusivos representaram 13,2% (14/106) no verão e 10,9% (7/64) no inverno. Também se observou que a mortalidade pré-abate nas duas épocas do ano avaliadas ocorre mais em suínos que estão no período de descanso (64,5% (139/216) do que durante o transporte (35,5% (77/216). / The present study evaluated the mortality of pigs just prior to slaughter through histopathological analysis in order to identify the causes of death. The study was conducted during the summer and winter of 2015 in a slaughter that has Federal Inspection Service in Rio Grande do Sul State located in Taquari Valley. During the summer, 141 deaths were accounted from the total deaths of 117 260 (0.12%), while, in the winter, it were 75 deaths from the total of 127.286 (0.05%). Of the 216 carcasses of dead animals in both periods, 170 were analyzed. Samples were examined in the laboratory of the Veterinary Pathology Sector of the Veterinary School of the Federal University of Rio Grande do Sul. Among the causes of death diagnosed, gastric ulcers in the esophageal quadrilateral region and pylorus were the most frequent, which represented 29.2% (31/106) in the summer and 32.8% (21/64) in winter. Pulmonary disorders such as enzootic pneumonia, influenza, bacterial pneumonia and pleuritis, were the second most frequent diagnosis, observed in 15.1% (16/106) in the summer and 18.8% (12/64) in the winter. Heart failure, including bacterial pericarditis, bacterial endocarditis, hypertrophic cardiomyopathy, myocarditis, myocardial infarction and neoplasia, had a frequency of 14.2% (15/106) in the summer and 9.4% (6/64) in the winter. Acute gastric dilatation caused by excess food in the stomach was also an important diagnosis, with 8.5% (9/106) in the summer and 4.7% (3/64) in the winter. Liver ruptures were observed in 5.7% of deaths (6/106) in summer and 7.8% (5/64) in the winter, while spleen ruptures were observed in 0.9% of deaths (1/106 ) in summer and 1.6% (1/64) in the winter, representing important diagnoses, however it is rarely reported in the literature as a cause of pig death. Proliferative enteropathy was diagnosed in 5.7% of the cases (6/106) in the summer and 4.7% (3/64) in the winter. Mesenteric torsion was diagnosed in 3.8% (4/106) of deaths in the summer and 6.2% (4/64) in the winter. Polyserositis were observed in lower frequency, 2.8% (3/106) of dead pigs in the summer and 3.1% (2/64) in the winter. Femur fracture was only observed in 0.9% of cases of death (1/106) in the summer period. Inconclusive cases accounted for 13.2% (14/106) in the summer and 10.9% (7/64) in the winter. It was also noted that pre-slaughter mortality in both seasons of the evaluated year occurs more in pigs that are in the rest period (64.5% (139/216) than during transportation (35.5% (77/216).

Este estudo foi desenvolvido para investigar os efeitos da suplementação dietética de cromo, da densidade no transporte para o frigorífico e da duração do descanso pré-abate sobre os indicadores de bem-estar, desempenho e qualidade de carne de ovinos confinados. Sessenta e quatro ovinos cruzados White Dorper x Santa Inês, foram divididos em dois grupos no confinamento: grupo controle e grupo que recebeu suplementação de 2 mg cromo orgânico diariamente. Durante as pesagens foram avaliados o ganho de peso, a reatividade dos animais por meio velocidade de fuga e da movimentação, intensidade de respiração e vocalização durante o manejo em balança, além do registro de variáveis climáticas. O transporte ao frigorífico foi realizado com duas densidades distintas, 0,2 m2 por animal e 0,3 m2 por animal. Foram aplicados dois períodos de descanso, de 7 e 14 horas, após o desembarque, antes do abate. Durante as pesagens do confinamento e o manejo pré-abate foram colhidas amostras de sangue para análise de cortisol, glicose e insulina. No frigorífico foram classificadas as carcaças quanto à presença de contusões, medidas as temperaturas e pH das carcaças às 1h e 24h, além de serem retiradas amostras do músculo Longissimus dorsi para análise da qualidade de carne. Para análise dos dados dessa etapa foi utilizado o procedimento Mixed do SAS utilizando-se tratamento, tempo, transporte e tempo de espera como efeito fixo e o sexo como efeito aleatório, assim como suas interações. Em caso de resultados significativos (P < 0,05) para as fontes de variações avaliadas nas análises de variância, foi adotado como procedimento para comparações múltiplas o Teste t de Student. Não foi verificado efeito significativo (P > 0,05) dos tratamentos estudados sobre os valores de desempenho, reatividade, contusão, características de carcaça, glicogênio muscular, extrato etéreo, características L* e a* da cor e perdas totais ao cozimento. Para as características de croma b* houve efeito significativo (P < 0,05) da suplementação de cromo, onde os animais que receberam cromo diariamente apresentaram um valor menor de b*. Para a maciez houve interação entre a suplementação de cromo e o tempo de espera. Os animais que receberam a suplementação diária de cromo apresentaram uma melhor maciez com o menor tempo de espera, diferente dos animais que não receberam a suplementação de cromo, que apresentaram uma melhor maciez com o maior tempo de espera. Para as análises de bilirrubina, fosfatase alcalina, insulina avaliadas durante o confinamento, não foi verificado efeito (P > 0,05) da suplementação de cromo diário, mas foi encontrado efeito (P < 0,0001) do tempo de confinamento sobre as médias de insulina. Além disso, foi encontrada uma interação (P < 0,0001) da suplementação de cromo com o tempo de confinamento para as médias de glicose. Para o cortisol verificou-se uma interação significativa (P = 0,0046) entre a suplementação de cromo e o tempo de confinamento, onde os animais que receberam a suplementação de cromo apresentaram menores valores de cortisol sanguíneo. Ainda, durante o manejo pré-abate foi observado efeito (P < 0,05) da densidade de transporte, onde os animais que foram transportados em menor densidade (0,3 m2.animal-1) apresentaram menores valores de cortisol. Após 7 horas de espera no abatedouro não houve diminuição da concentração dos níveis séricos de cortisol (P > 0,05), porém, após 14 horas de espera observou-se uma queda significativa desses níveis (P < 0,001). Com esses resultados podemos concluir que a suplementação de cromo não influenciou nas características de desempenho e reatividade, porém, melhorou a maciez em um menor tempo de espera. A densidade de transporte não alterou a qualidade da carne, mas influenciou no bem-estar dos animais. O período de descanso de 14 horas antes do abate diminui o estresse e os níveis séricos de cortisol. / The aim of this study was to investigate the influence of chromium supplementation, the density in transport to the slaughterhouse and the duration of resting periods before slaughter, on the indicators of welfare, growth and meat quality of individual feedlot lambs. Sixty four crossbred White Dorper breed with Santa Ines were divided into two groups in confinement: control group and the group that received daily supplementation of 2 mg organic chromium. During the weighing weight gain were evaluated, as the reactivity of the animals through the flight velocity and movement, intensity of respiration and vocalization during handling in balance, as well as recording of climatic variables. The transport to the slaughterhouse was performed with two different densities, 0.2 m2 and 0.3 m2 per animal. Two resting periods of 7 and 14 hours were applied after transport, before slaughter. During confinement weighing and the pre-slaughter management blood samples were collected for cortisol, glucose and insulin analysis. Carcasses were classified for the presence of bruises and measurement of the temperature and pH at 0 and 24 hours, and samples of the Longissimus dorsi muscle were collected for meat quality analysis. Data analysis used mixed procedure of SAS using treatment, time, transportation and resting period as fixed effect and random effect the sex as well as their interactions. In case of significant results (P < 0.05) of data evaluated in the procedure of analysis of variance it was adopted for multiple comparisons the Student t test. No effect was observed (P > 0.05) for the treatments on the values of performance, reactivity, contusion, carcass characteristics, muscle glycogen, lipids, and features L* color a* and total cooking losses. For the characteristics of b* it was found a significant effect (P < 0.05) for chromium supplementation, with lower values of b*. To the tenderness it was found an interaction between supplementation and resting period, and the animals that received daily supplementation of chromium showed better tenderness with shorter resting periods, different from animals that received no supplementation which showed better tenderness with longest resting periods. For the analysis of bilirubin, alkaline phosphatase, insulin evaluated during confinement, no significant effect was observed (P > 0.05) of daily supplemental chromium, but no effect of insulin was found (P < 0.0001) over time confinanent. Furthermore, it was found an interaction (P < 0.0001) of supplementation time for glucose values. For cortisol, there was a significant interaction (P = 0.0046) between chromium supplementation and confinement time, where animals that received supplementation had lower levels of blood cortisol. Still, during the pre-slaughter management it was observed a significant effect (P < 0.05) of the density of transport, where the animals that were transported in smaller density (0.3 m2.animal-1) showed lower values of cortisol. After 7 hours of resting period in the slaughterhouse, there was no decrease in the concentration of serum cortisol (P > 0.05 ), but after 14 hours it was observed a significant decrease in these levels (P < 0.001). With these results it can be conclude that chromium supplementation did not affect the performance characteristics and reactivity, however, improved tenderness in a shorter resting period. The density of transport did not alter the meat quality, but influenced the welfare of animals. The resting period before slaughter decreases stress and serum cortisol levels when the period is higher than 7 hours.

Les acouphènes subjectifs chroniques concernent entre 10 et 15% de la population des pays industrialisés. Ils peuvent entraîner des modifications visibles du comportement, une détérioration très nette de la qualité de vie et dans des cas extrêmes des troubles nerveux post-traumatiques ou un état dépressif clinique (Berrios & Rose, 1992; Berrios et al, 1988) pouvant mener à des pensées suicidaires (Dobie, 2003). Les acouphènes peuvent provenir de différents relais des voies auditives périphériques ou centrales, cependant la grande majorité des acouphènes chroniques est liée à une perte auditive, presbyacousie, ou exposition au bruit. En effet, approximativement 90% des acouphènes chroniques sont liés à une perte auditive (Nicolas-Puel et al. 2006).Les acouphènes peuvent entraîner des changements importants dans le fonctionnement de certains réseaux cérébraux. Même en cas de lésion périphérique, l’anomalie perceptive qui en résulte peut à terme entraîner une modification de l’activité des structures cérébrales, par des phénomènes de plasticité. Malheureusement aujourd’hui compte tenu des divergences constatées aux niveaux des résultats obtenus par les différentes études effectuées chez les sujets acouphéniques, aucun consensus n’a pu être établi quant à l’établissement d’un modèle de la physiopathologie des acouphènes liés à une perte auditive.L’objectif général de ce travail est donc de mettre en place un protocole multimodal robuste afin de détecter des d’anomalies d’activation cérébrales chez des sujets souffrants d’acouphènes unilatéraux liés à une perte auditive par rapport à des sujets normo-entendants. Ce protocole comprend :- un paradigme permettant de réaliser des acquisitions fonctionnelles avec et sans acouphènes perçus, grâce à l’inhibition résiduelle des acouphènes,- un paradigme d’IRM fonctionnelle de repos,- un paradigme d’IRM fonctionnelle avec stimulation sonores,- une mesure du débit sanguin cérébral régional.Notre étude a permis de mettre en évidence l’implication du réseau du mode par défaut et notamment du précunéus dans la perception d’acouphènes. En effet, les résultats de notre étude montrent selon plusieurs modalités que ce réseau est hypo-activé chez les sujets présentant des acouphènes liés à une perte auditive. L’hypoactivité de ces régions pourrait être réduite de façon temporaire par le masquage des acouphènes par une stimulation sonore. De plus, l’inhibition résiduelle des acouphènes conduit à l’hyper-activations des régions du réseau du mode par défaut et notamment du précunéus. / Chronic subjective tinnitus concern 10 to 15% of the population in industrialized countries. They can cause visible changes in behavior, a sharp deterioration in the quality of life and in extreme cases of post-traumatic stress disorder or clinical depression (Berrios & Rose, 1992; Berrios et al, 1988) that could lead to suicidal thoughts (Dobie, 2003). Tinnitus may originate from different peripherical nodes or central auditory pathways, however the majority of chronic tinnitus is associated with hearing loss, presbycusis, or exposure to noise. Indeed, approximately 90% of chronic tinnitus is associated with hearing loss (Nicolas-Puel et al. 2006).Tinnitus can cause significant changes in the activity of brain networks. Even in case of peripherical lesions, the perceptual abnormality that results can ultimately lead to a change in the activity of brain structures, by plasticity phenomena. Unfortunately today given the discrepancies in the levels of results obtained by different studies in the affected persons, no consensus has been established regarding the establishment of a model of the pathophysiology of tinnitus associated with a loss hearing.The general objective of this work is to develop a robust multimodal protocol to detect cerebral activation abnormalities in subjects suffering from unilateral tinnitus associated with hearing loss compared to normal-hearing subjects. This protocol includes:- An acquisition paradigm with and without perceived tinnitus through the residual inhibition,- A resting state fMRI paradigm,- A sound evoked fMRI paradigm (with sound stimulation),- A measure of the regional cerebral blood flow.Our study has permitted to highlight the involvement of the default mode network including the precuneus in the perception of tinnitus. Indeed, the results of our study show as many terms as the network is hypo-activated in subjects with tinnitus associated with hearing loss. Hypoactivity of these areas could be reduced temporarily by masking the tinnitus by sound stimulation. In addition, residual inhibition of tinnitus leads to hyper-activation regions of the default mode of the network and in particular precuneus.

There is a high prevalence in malnutrition among traumatic brain injury (TBI) due to the hypermetabolism and hypercatabolism which develop post injury. Traumatic brain injury patients are different, even among themselves, in their energy requirements and response to nutritional therapy. This implies that there are other factors that affect the energy intake of these patients and enhance the incidence of malnutrition. This dissertation study examines the nutritional status of TBI patients upon admission to the intensive care unit (ICU) and during their hospital stay to describe baseline status, detect changes in nutritional status over 7 days, and identify the factors affecting the adequacy of energy intake and the change in nutritional status as a consequence. Anthropometric measurements, biomedical measurements, measures of severity of illness, daily health status, level of brain injury severity, and other data were collected from the medical records of 50 patients, who were ≥ 18 years old, mechanically ventilated in the first 24 hours of ICU admission, and had a Glasgow Coma Scale score between 3-12. These data were used to examine the previous relationships. Although there was no statistically significant change found in body mass index and weight, there was a significant change detected in other nutritional markers, including hemoglobin, albumin, and total lymphocyte levels over the 7 days of ICU and hospital stay. No significant relationship was found between the adequacy of energy intake and total prescribed energy, severity of illness, level of brain injury severity, daily health status, patient age, intracranial pressure, or time of feeding initiation. Findings may be used to develop and test interventions to improve nutritional status during the acute phase of TBI. This will lay a foundation for health care providers, including nurses, to establish standards for practice and nutrition protocols to assure optimal nutrition assessment and intervention in a timely manner.

Introduction: Weight loss programs are based on inducing a negative energy balance by decreasing energy intake while increasing energy expenditure. Energy needs of obese patients are difficult to determine. The value of resting energy expenditure, as the largest component of the energy needs, is usually calculated to asses an adequate energy intake for obese patient. In clinical practice, predictive equations are most commonly used for this purpose, because of their simplicity, although many clinical studies have shown that in obese individuals they may generate errors large enough to impact the outcome of treatment. It leads to the prescription of an inadequate diet that does not meet the criterion of long-term sustainability. Objective: The aim of the thesis is to compare the values of resting energy expenditure (REE) measured by indirect calorimetry with values calculated with Harris-Benedict predictive equation in a selected group of obese individuals. Methods: The sample includes 38 subjects, 28 women and 10 men, patients of the General University Hospital in Prague. The average age is 48 ± 11,71 years, the mean BMI is 42,88 ± 9,09 kg/m2 . For each subject, resting energy expenditure was measured by indirect calorimetry and calculated by the Harris-Benedict predictive equation. Indirect...

La mémoire de reconnaissance nous permet à la fois de détecter rapidement un stimulus précédemment perçu (familiarité), et de récupérer des informations relatives au contexte de notre rencontre avec ce stimulus (recollection). Les modèles neuro-anatomiques d'Aggleton et Brown (1999) puis d'Aggleton et al. (2011) postulent que le noyau antérieur (NA) du thalamus et le tractus mamillo-thalamique (TMT) du fait de leurs connexions avec l'hippocampe font partie du circuit de la recollection tandis que le noyau dorso-médian (DM) participerait à la familiarité en raison de ses connexions avec le cortex périrhinal. Dans cette thèse nous avons testé cette hypothèse d'indépendance. 12 patients avec un infarctus thalamique gauche ont été recrutés ainsi qu'un groupe de sujets contrôles appariés. Tous les participants ont été soumis à un bilan neuropsychologique, à trois tâches expérimentales de mémoire de reconnaissance et à un examen d'IRM morphologique et d'IRM fonctionnelle de repos. Selon les tâches nous avons estimé la contribution de la recollection et de la familiarité à la réponse sur la base de la verbalisation de la source, du degré de confiance dans la réponse ou de la catégorisation des réponses. Les lésions thalamiques ont été quantifiées et localisées automatiquement grâce à une nouvelle approche méthodologique que nous avons développée. Le profil neuropsychologique des patients a mis en évidence une amnésie antérograde verbale et un trouble exécutif modéré (Etude 1). Les lésions atteignaient principalement le DM alors que le NA était intact chez tous. Le TMT était lésé chez les 7 patients les plus amnésiques (Etudes 1 et 2). La recollection était altérée chez les patients quelle que soit la tâche alors que la familiarité était préservée. De plus l'indice de recollection corrélait avec la lésion du DM (Etude 2). Enfin, des corrélations ont été trouvées dans l'étude en connectivité fonctionnelle entre la disconnexion thalamo-frontale et la recollection (Etude 3). En somme, ces résultats signifient i\ qu'une lésion du NA n'est pas nécessaire pour causer une amnésie ii\ qu'une lésion du DM est suffisante pour causer un défaut de recollection mais pas nécessaire pour atteindre la familiarité iii\ qu'une lésion du TMT prédit une amnésie sévère, enfin iv\ que le réseau reliant fonctionnellement le DM au cortex préfrontal semble être impliqué dans l'expérience subjective de la mémoire de reconnaissance plutôt que dans ses contenus. Ils suggèrent de plus que le modèle d'Aggleton et al (2011) devrait être révisé en ce qui concerne la relation familiarité / DM. / Recognition memory allows determining whether a stimulus has been previously encountered based on either a rapid detection process (familiarity) or a longer retrieval of the context associated with the stimulus (recollection). Aggleton and Brown's model (1999) and Aggleton and colleagues (2011) postulated that recollection and familiarity are anatomically and functionally independent. They hypothesized that the anterior nucleus (AN) / mamillothalamic tract (MTT) complex of the thalamus would be critical for recollection due to its connections with the hippocampus. The Mediodorsal (MD) nucleus would support familiarity owing to its links with the perirhinal cortex. In this thesis we tested this independence hypothesis. The 12 subjects with a pure left thalamic infarction were included along with a healthy matched control group. Every subject underwent a neuropsychological assessment, three experimental verbal recognition memory tasks, a high-resolution structural volumetric MRI scan and resting state functional imaging. Recollection and familiarity estimations were derived from subjective reports or responses categorization. We specifically developed the methods used to automatically analyse the volume and localization of the lesions. Patients performed worse than controls on verbal memory and to a lesser extent on executive tasks (Study 1). Most of the lesions were located in the MD while no lesion of the AN was found. The seven patients exhibiting MTT damage had the lowest memory performance (Studies 1 and 2). Recollection was lower in patients than in controls in all the three tasks whereas familiarity was systematically normal. In addition we found a significant correlation between the recollection index and the DM damage, suggesting that DM is directly involved in recollection (Article 2). Finally the functional connectivity results showed a correlation between recollection and a pattern of thalamofrontal disconnection in the patients, helping to understand the DM-recollection relationship. Overall, the findings of the different studies mean that i\ AN damage is rare and is not necessary to cause an amnesia, ii\ MD damage is sufficient to cause a recollection impairment but not necessary to impair familiarity, iii\ MTT damage predicts the severity of the amnesia, iv\ the network linking functionally the MD with the prefrontal cortex seems to be involved in the subjective experience associated with recognition memory.

Converging evidence from a variety of fields, including psychiatry, suggests that the temporal correlates of the brain’s resting state could serve as essential markers of a healthy and efficient brain. We use ketamine to induce schizophrenia-like states in 32 healthy individuals to examine the brain’s resting states using fMRI. We found a global reduction in temporal variability quantified by the time series’ standard deviation and an increase in scale-free properties quantified by the Hurst exponent representing the signal self-affinity over time. We also found network-specific and frequency-specific effects of ketamine on these temporal measures. Our results confirm prior studies in aging, sleep, anesthesia, and psychiatry suggesting that increased self-affinity and decreased temporal variability of the brain resting state could indicate a compromised and inefficient brain state. Our results expand our systemic view of the temporal structure of the brain and shed light on promising biomarkers in psychiatry

Introduction: The aim of the project was to investigate the effects of antidepressants on brain networks whilst at rest. My hypothesis was that antidepressants work by reversing persistent activity in the brain’s default mode network (DMN). The DMN is implicated in self-reflection and rumination in MDD. The methodologies and results of studies of resting state networks in MDD and the effects of antidepressants are reviewed in the thesis. Increasing evidence implicates glutamate in the action of antidepressant drugs. Whether there are illness related changes in glutamate function is unresolved, largely because of the lack of techniques for assessing it. Ketamine and other NMDA antagonists have improved MDD symptoms within 24 hours though the effects are short lasting. The molecular neural networks involved in ketamine’s putative antidepressant effects are unclear. The thesis reviews the evidence. Much evidence implicates ACC as a site of action of antidepressant effects but whether this is through its regulation of the DMN or other networks is not known. This thesis compares the effect of ketamine and citalopram on ACC-related systems. Method: The thesis combines two systematic reviews of the effects of MDD and antidepressant drugs on i) resting state networks (53 studies) and ii) glutamate neurotransmission (45 studies of clinical efficacy of ketamine). There are two experimental chapters. The first describes investigation into two rapid acting antidepressant drugs acting via glutamate mechanisms. 54 unmedicated cMDD were scanned across two centres on 3T MRI scanners while being infused with placebo (0.5% saline), 0.5mg/kg ketamine or 100mg AZD6765 over 1 hour. fMRI resting state data between drug treatments was compared for the final 25 minutes of the drug infusion and for a 25 minute resting state scan a day later. The second experimental chapter examines whether these effects were shared by citalopram, a standard antidepressant. 67 unmedicated cMDD, rMDD and HC were administered citalopram 7.5mg i.v. and scanned on a 1.5T MRI scanner. In a second study 63 cMDD and HC were administered i.v. citalopram 7.5mg or placebo (0.5% saline). fMRI resting state data for the final 12 ½ minutes following drug infusion was compared. Independent Component Analysis was performed using the Group ICA for fMRI toolbox. The resting component with the highest spatial correlation to the ACC was used. Brain maps of the intensity of the selected component were constructed for each individual. Group averages were calculated and compared using SPM. Regional analysis was performed using Marseille Boite a Regions d'interet. Results: On day 1 AZD6765 significantly increased mean intensity of ACC resting component in the right insula, right IPL and left cingulate gyrus greater than ketamine or placebo. Ketamine increased mean intensity of ACC resting component greater than placebo in the right lentiform nucleus and left mFG. Significantly decreased mean intensity of ACC resting component in the left insula in the AZD6765 group compared to placebo was noted. On day 2 AZD6765 increased mean intensity of ACC resting component greater than ketamine and placebo in the left and right lentiform nuclei. AZD6765 reduced mean intensity of the ACC resting component in the left and right MFG. The first citalopram study revealed reduced mean intensity of ACC resting component in cMDD compared to rMDD and HC in PCC. rMDD had reduced mean intensity of ACC resting component in the precuneus compared to HC. In the second study, citalopram had no effect in HC but normalised precuneus activity in cMDD producing a significant drug x group interaction. Conclusions: The acute antidepressant effects of citalopram are modulated by changes in the bilateral precuneus. The precuneus is central to connectivity with other regions in MDD. It has a prominent role in the DMN and is linked to rumination. The mechanism of the antidepressant effects of AZD6765 is different from those of ketamine and citalopram. The insula, IPL, MFG, cingulate gyrus and lentiform nuclei are all regions implicated in MDD suggesting antidepressant effects. The rapid antidepressant effects of AZD6765 are possibly due to a resetting of the interface between DMN and salience networks.