Attention Deficit Hyperactivity Disorder (ADHD) is a disorder affecting cognitive control. These functions are important to achieve goals when different actions need to be executed in close succession. This type of multi-component behavior, which often further requires the processing of information from different modalities, is important for everyday activities. Yet, possible changes in neurophysiological mechanisms have not been investigated in adolescent ADHD. We examined N = 31 adolescent ADHD patients and N = 35 healthy controls (HC) in two Stop-Change experiments using either uni-modal or bi-modal stimuli to trigger stop and change processes. These stimuli were either presented together (SCD0) or in close succession of 300 milliseconds (SCD300). Using event-related potentials (ERP), EEG data decomposition and source localization we analyzed neural processes and functional neuroanatomical correlates of multicomponent behavior. Compared to HCs, ADHD patients had longer reaction times and higher error rates when Stop and Change stimuli were presented in close succession (SCD300), but not when presented together (SCD0). This effect was evident in the uni-modal and bi-modal experiment and is reflected by neurophysiological processes reflecting response selection mechanisms in the inferior parietal cortex (BA40). These processes were only detectable after accounting for intra-individual variability in neurophysiological data; i.e. there were no effects in standard ERPs. Multi-component behavior is not always deficient in ADHD. Rather, modulations in multi-component behavior depend on a critical temporal integration window during response selection which is associated with functioning of the inferior parietal cortex. This window is smaller than in HCs and independent of the complexity of sensory input.

Choisir quel mouvement effectuer est une fonction primordiale du système nerveux central. Comment ces décisions sont prises est encore sujet à débats. Une hypothèse traditionnelle pose qu’elles sont prises de façon sérielle, à l’aide de processus perceptifs qui alimentent un exécutif central, qui communique ensuite au système moteur quel mouvement effectuer. L’hypothèse alternative préférée par notre équipe est que les mouvements potentiels commencent à être préparés en parallèle et entrent en compétition pour les effecteurs. Dans le but de tester ces hypothèses, notre équipe a enseigné à un macaque une tâche de prise de décision motrice. Le sujet y est placé devant un écran où deux cibles apparaissent. Chacune a une valeur qui découle de deux caractéristiques : sa luminosité (BU pour bottom-up, information ascendante) et l’orientation d’une ligne qui la coupe comme une aiguille d’horloge (TD pour top-down, information descendante.) Le sujet choisit une des deux à l’aide d’un mouvement d’atteinte, et reçoit une récompense proportionnelle à sa valeur. Cette tâche permet de comparer plusieurs types d’essais : certains présentent une seule cible, une absence de choix, ou deux cibles identiques, un choix sans conséquence. D’autres ont une cible plus valable que l’autre, le choix est alors facile. On peut alors faire varier la caractéristique (BU ou TD) qui donne une plus grande valeur à la meilleure cible. Finalement, on peut montrer deux cibles de valeur égale, mais dont une tire sa valeur d’un bon score TD et l’autre, d’un bon score BU. Le sujet doit alors, en quelque sorte, choisir entre les caractéristiques. Pendant que le sujet exécute la tâche, on enregistre ses potentiels de champ locaux (LFP) à l’aide de deux réseaux d’électrodes déplaçables individuellement, l’un placé dans le cortex pariétal postérieur (PPC) et l’autre, dans le cortex prémoteur dorsal (PMd). L’analyse de ces données à l’aide de spectrogrammes, et une discussion des réactions spécifiques dans les bandes de fréquences alpha, bêta et gamma, sont présentées ici. / Choosing which movement to make is a primary function of the central nervous system. How these decisions are made is still a matter of debate. A traditional hypothesis posits that such decisions are made in a serial fashion: perceptual processes feed into a central executive, which then communicates to the motor system which movement to make. The alternative hypothesis preferred by our team is that potential movements begin to be prepared in parallel, and compete for effectors until a consensus forms in brain areas related to controlling the movements. In order to test these hypotheses, our team taught a macaque to perform a reach-based decision-making task. The subject is placed in front of a screen on which two targets appear. Each target has a value derived from two features: its brightness (BU, bottom-up information) and the orientation of a line that crosses it like a clock hand (TD, top-down information.) The subject freely chooses one of the two targets by reaching it, and then receives a reward proportional to its value. This task compares several types of trials: some show a single target, therefore no choice, or show two identical targets, which means the choice has no consequences. Other trials have one target that is more valuable than the other, which makes the choice easy. The feature which gives that better target a greater value can be either BU or TD. Finally, some trials show two targets of equal value, but one of them derives its value from a good TD score while the other derives its value from a good BU score. The subject must then choose between the features. While the subject performs the task, local field potentials (LFP) are recorded using two individually movable electrode arrays. One array is placed in the posterior parietal cortex (PPC) and the other, in the dorsal premotor cortex (PMd). The data thus obtained is analyzed using spectrograms, and a discussion of specific responses in the alpha, beta, and gamma frequency bands is presented here.

Objective: Type 1 diabetes is associated with autoantibodies to different organs that include the gut. The objective of the study was to determine the risk of developing gastric parietal cell autoimmunity in relation to other autoimmunity in individuals with a family history of type 1 diabetes. Methods: Autoantibodies to the parietal cell autoantigen, H+/K+ ATPase subunit A (ATP4A) was measured in 2218 first-degree relatives of patients with type 1 diabetes, who were prospectively followed from birth for a median of 14.5 years. All were also tested regularly for the development of islet autoantibodies, transglutaminase autoantibodies, and thyroid peroxidase autoantibodies. Results: The cumulative risk to develop ATP4A autoantibodies was 8.1% (95% CI, 6.6–9.6) by age 20 years with a maximum incidence observed at age 2 years. Risk was increased in females (HR, 1.9; 95% CI, 1.3–2.8; p = 0.0004), relatives with the HLA DR4-DQ8/DR4-DQ8 genotype (HR, 3.4; 95% CI, 1.9–5.9; p < 0.0001) and in participants who also had thyroid peroxidase autoantibodies (HR, 3.7; 95% CI, 2.5– 5.5; p < 0.0001). Risk for at least one of ATP4A-, islet-, transglutaminase-, or thyroid peroxidase-autoantibodies was 24.7% (95% CI, 22.6–26.7) by age 20 years and was 47.3% (95% CI, 41.3–53.3) in relatives who had an HLA DR3/DR4-DQ8, DR4-DQ8/ DR4-DQ8, or DR3/DR3 genotype (p < 0.0001 vs. other genotypes). Conclusions: Relatives of patients with type 1 diabetes who have risk genotypes are at very high risk for the development of autoimmunity against gastric and other organs.

INTRODUÇÃO: Apesar da importância dos medicamentos antidepressivos no tratamento dos transtornos de humor e de ansiedade, sua ação sobre sistemas cerebrais responsáveis pela expressão emocional ainda não foram claramente estabelecidos. Estudos recentes têm examinando o sinal dependente de nível de oxigenação sanguínea (do inglês, \"BOLD\") durante estímulos emocionais em indivíduos saudáveis sob uso de antidepressivos. Nesse estudo, pretendemos estender essa avaliação às alterações do humor e comportamento emocional devido ao uso prolongado de um antidepressivo bloqueador de serotonina e noradrenalina em pessoas saudáveis. MÉTODOS: foram selecionados dezesseis voluntários, sem antecedentes psiquiátricos pessoais ou familiares, que participaram de um ensaio farmacológico simples-cego de quatro semanas de doses baixas de clomipramina (até 40 mg/dia). Ao final desse período, dez sujeitos foram selecionados como não responsivos, e os restantes seis sujeitos foram selecionados como responsivos por apresentarem claras mudanças em três dos quatro seguintes critérios: tolerância interpessoal, eficiência, bem estar, e mudança substancial em sua auto percepção. O grupo de sujeitos classificados como responsivos foram submetidos a um ensaio controlado duplo-cego confirmatório. A aquisição de imagens cerebrais ocorreu após quatro semanas de uso de medicação (simples cego) e quatro semanas após a sua suspensão, ao final da participação no ensaio farmacológico. O imageamento cerebral foi realizado durante a indução de estados afetivos de felicidade, irritabilidade e neutros por relatos autobiográficos. A resposta emocional desses estados foi obtida por escalas de auto avaliação de ansiedade, irritabilidade e felicidade. As diferenças de sinal entre os estados afetivos foram utilizadas para a análise estatística da interação dos efeitos estado medicamentoso e grupo por testes ANOVA. RESULTADOS: Foi encontrada uma interação significativa entre o efeito de grupo e o estado medicamentoso sobre os estados afetivos de irritabilidade, mas não sobre os de felicidade. Se observou redução na auto avaliação de ansiedade no grupo responsivo com o uso de medicação na diferença entre os estados induzidos de irritabilidade e felicidade, em comparação com o efeito no grupo não responsivo; e também, redução na auto avaliação de felicidade com o uso de clomipramina na totalidade da amostra, na diferença entre o estados induzidos de irritabilidade e neutro. A alteração sobre o efeito BOLD (p < 0,005) foi localizada em regiões adjacentes à junção frontoparietal para a indução de irritabilidade em relação à felicidade e em relação aos estados neutros, no grupo responsivo em relação ao não responsivo, durante o período em uso relativo àquele sem uso de clomipramina, e na junção têmporo-paríeto-occipital, exclusivamente para a diferença irritabilidade-felicidade. CONCLUSÕES: a modificação favorável que sujeitos saudáveis apresentaram ao uso prolongado de um antidepressivo bloqueador da serotonina e noradrenalina, pode estar relacionada à modificação no processamento cerebral da memória autobiográfica de emoções negativas / INTRODUCTION: despite the importance of antidepressant agents to the treatment of anxiety and depressive disorders, there is not yet a clear understanding of their actions upon specific brain systems relevant to emotional processing. Recent studies have examined blood oxygen level dependent (BOLD) signal during emotion stimuli in healthy individuals in antidepressant use. The study intends to extend these measures to the changes over mood and emotional behavior by prolonged use of a serotonin and noradrenaline blocker antidepressant. METHODS: we selected sixteen subjects, with no personal or family history of psychiatric disorders, which participated of a four-week single-blind trial with low doses of clomipramine (up to 40mg/day). After this period, ten subjects were classified as non responsives, the remaining six subjects being classified as responsives because clomipramine provided positive changes in three of four of the following criteria: interpersonal tolerance, self-efficacy, mood and self-perception of a substantial change. Responsives were included in a placebo-controlled confirmatory trial. Imaging sessions occurred at the end of the four-week course of clomipramine and again after a four-week clomipramine washout period, at the end of pharmacological trial. Subjects were scanned during the induction of irritability, happiness and neutral affective states by autobiographical recall. Self-report assessment was performed for each induction by anxiety, irritability and happiness scales. Inter-condition differences (affective induction) were used in the analysis of interaction of medication status and group effects by ANOVA tests. RESULTS: A significant interaction was found between group and treatment during irritability, but not during happiness emotions. It was observed a reduction in the scale of self-evaluation of anxiety in responsive group with the use of medication to the difference between irritability-happiness states, compared to the non responsive group; and a reduction in auto evaluation of happiness, in the totality of the sample in use of clomipramine, in difference irritability-neutral. There was a significant increase of BOLD effect in the responsive group during use relative to the period without use of clomipramine, compared to the effect on non-responsive group (p < 0.005). This effect was located in regions that surround the frontoparietal junction to the irritability relative to happiness and to irritability relative to neutral induction, and in the temporo-parieto-occipital junction, exclusively to the irritability relative to happiness induction. CONCLUSIONS: The favorably changes in healthy subjects who respond to prolonged serotonin and noradrenaline blocker use, may relate to changes in neural processes of autobiographical memory of negative emotions

INTRODUÇÃO: Apesar da importância dos medicamentos antidepressivos no tratamento dos transtornos de humor e de ansiedade, sua ação sobre sistemas cerebrais responsáveis pela expressão emocional ainda não foram claramente estabelecidos. Estudos recentes têm examinando o sinal dependente de nível de oxigenação sanguínea (do inglês, \"BOLD\") durante estímulos emocionais em indivíduos saudáveis sob uso de antidepressivos. Nesse estudo, pretendemos estender essa avaliação às alterações do humor e comportamento emocional devido ao uso prolongado de um antidepressivo bloqueador de serotonina e noradrenalina em pessoas saudáveis. MÉTODOS: foram selecionados dezesseis voluntários, sem antecedentes psiquiátricos pessoais ou familiares, que participaram de um ensaio farmacológico simples-cego de quatro semanas de doses baixas de clomipramina (até 40 mg/dia). Ao final desse período, dez sujeitos foram selecionados como não responsivos, e os restantes seis sujeitos foram selecionados como responsivos por apresentarem claras mudanças em três dos quatro seguintes critérios: tolerância interpessoal, eficiência, bem estar, e mudança substancial em sua auto percepção. O grupo de sujeitos classificados como responsivos foram submetidos a um ensaio controlado duplo-cego confirmatório. A aquisição de imagens cerebrais ocorreu após quatro semanas de uso de medicação (simples cego) e quatro semanas após a sua suspensão, ao final da participação no ensaio farmacológico. O imageamento cerebral foi realizado durante a indução de estados afetivos de felicidade, irritabilidade e neutros por relatos autobiográficos. A resposta emocional desses estados foi obtida por escalas de auto avaliação de ansiedade, irritabilidade e felicidade. As diferenças de sinal entre os estados afetivos foram utilizadas para a análise estatística da interação dos efeitos estado medicamentoso e grupo por testes ANOVA. RESULTADOS: Foi encontrada uma interação significativa entre o efeito de grupo e o estado medicamentoso sobre os estados afetivos de irritabilidade, mas não sobre os de felicidade. Se observou redução na auto avaliação de ansiedade no grupo responsivo com o uso de medicação na diferença entre os estados induzidos de irritabilidade e felicidade, em comparação com o efeito no grupo não responsivo; e também, redução na auto avaliação de felicidade com o uso de clomipramina na totalidade da amostra, na diferença entre o estados induzidos de irritabilidade e neutro. A alteração sobre o efeito BOLD (p < 0,005) foi localizada em regiões adjacentes à junção frontoparietal para a indução de irritabilidade em relação à felicidade e em relação aos estados neutros, no grupo responsivo em relação ao não responsivo, durante o período em uso relativo àquele sem uso de clomipramina, e na junção têmporo-paríeto-occipital, exclusivamente para a diferença irritabilidade-felicidade. CONCLUSÕES: a modificação favorável que sujeitos saudáveis apresentaram ao uso prolongado de um antidepressivo bloqueador da serotonina e noradrenalina, pode estar relacionada à modificação no processamento cerebral da memória autobiográfica de emoções negativas / INTRODUCTION: despite the importance of antidepressant agents to the treatment of anxiety and depressive disorders, there is not yet a clear understanding of their actions upon specific brain systems relevant to emotional processing. Recent studies have examined blood oxygen level dependent (BOLD) signal during emotion stimuli in healthy individuals in antidepressant use. The study intends to extend these measures to the changes over mood and emotional behavior by prolonged use of a serotonin and noradrenaline blocker antidepressant. METHODS: we selected sixteen subjects, with no personal or family history of psychiatric disorders, which participated of a four-week single-blind trial with low doses of clomipramine (up to 40mg/day). After this period, ten subjects were classified as non responsives, the remaining six subjects being classified as responsives because clomipramine provided positive changes in three of four of the following criteria: interpersonal tolerance, self-efficacy, mood and self-perception of a substantial change. Responsives were included in a placebo-controlled confirmatory trial. Imaging sessions occurred at the end of the four-week course of clomipramine and again after a four-week clomipramine washout period, at the end of pharmacological trial. Subjects were scanned during the induction of irritability, happiness and neutral affective states by autobiographical recall. Self-report assessment was performed for each induction by anxiety, irritability and happiness scales. Inter-condition differences (affective induction) were used in the analysis of interaction of medication status and group effects by ANOVA tests. RESULTS: A significant interaction was found between group and treatment during irritability, but not during happiness emotions. It was observed a reduction in the scale of self-evaluation of anxiety in responsive group with the use of medication to the difference between irritability-happiness states, compared to the non responsive group; and a reduction in auto evaluation of happiness, in the totality of the sample in use of clomipramine, in difference irritability-neutral. There was a significant increase of BOLD effect in the responsive group during use relative to the period without use of clomipramine, compared to the effect on non-responsive group (p < 0.005). This effect was located in regions that surround the frontoparietal junction to the irritability relative to happiness and to irritability relative to neutral induction, and in the temporo-parieto-occipital junction, exclusively to the irritability relative to happiness induction. CONCLUSIONS: The favorably changes in healthy subjects who respond to prolonged serotonin and noradrenaline blocker use, may relate to changes in neural processes of autobiographical memory of negative emotions

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Numerical cognition has been shown to share many aspects of spatial cognition, both behavioural and neurological. However, it is unclear whether a particular type of spatial cognition, visuospatial mental imagery (VSMI), may play a role in symbolic numerical representation. In this thesis, I first show that mental rotation, a form of VSMI, is related to two measures of basic numerical representation. I then show that number-space synaesthesia (NSS), a rare type of VSMI involving visualised spatial layouts for numbers, does not show an advantage in mental rotation, but shows interference in number line mapping. I next present a study investigating links between NSS and the ability to learn novel numerical symbols. I demonstrate that NSS shows an advantage at learning novel numerals, and that transcranial random noise stimulation, which increases cortical excitability, confers broadly similar advantages that nonetheless differ in subtle ways. I present a study of transcranial alternating current stimulation on the same symbol learning paradigm, which fails to demonstrate effects. Lastly, I present data showing that strength of numerical representation in these newly-learnt symbols is correlated with a measure of mental rotation, and also with visual recognition ability for the symbols after, but not before, training. All together, these findings suggest that VSMI does indeed play a role in numerical cognition, and that it may do so from an early stage of learning symbolic numbers.

Cette thèse vise à modéliser les instabilités hydrodynamiques générant des détachements tourbillonnaires pariétaux (ou VSP) responsables des Oscillations De Pression dans les moteurs à propergol solide longs et segmentés par interaction avec l’acoustique du moteur. Ces instabilités sont modélisées en tant que modes de stabilité linéaire globaux de l’écoulement d’un conduit à parois débitantes. En supposant que les structures pariétales émergent d’une perturbation de l’écoulement de base, des modes discrets et indépendants du maillage utilisé sont calculés. Dans ce but, une discrétisation par collocation spectrale multi-domaine est implémentée dans un solveur parallèle afin de s’affranchir de la croissance polynomiale des fonctions propres et de la présence de couches limites. Les valeurs propres ainsi calculées dépendent explicitement des frontières du domaine, à savoir la position de la perturbation et celle de la sortie, et sont ensuite validées par simulation numérique directe. On montre alors qu’elles permettent bien de décrire la réponse à une perturbation initiale de l’écoulement modifié par une rupture de débit pariétale. Ensuite, la simulation d’une réponse forcée par l’acoustique se fait sous forme de structures tourbillonnaires dont les fréquences discrètes sont en accord avec celles des modes de stabilité. Ces structures sont réfléchies en ondes de pression de même fréquences remontant l’écoulement. Finalement, la simulation numérique et la théorie de la stabilité permettent de montrer que le VSP, dont la réponse est linéaire vis-à-vis d’un forçage compressible comme l’acoustique, est le phénomène moteur des Oscillations De Pression. / The current work deals with the modeling of the hydrodynamic instabilities that play a major role in the triggering of the Pressure Oscillations occurring in large segmented solid rocket motors. These instabilities are responsible for the emergence of Parietal Vortex Shedding (PVS) and they interact with the boosters acoustics. They are first modeled as eigenmodes of the internal steady flowfield of a cylindrical duct with sidewall injection within the global linear stability theory framework. Assuming that the related parietal structures emerge from a baseflow disturbance, discrete meshindependant eigenmodes are computed. In this purpose, a multi-domain spectral collocation technique is implemented in a parallel solver to tackle numerical issues such as the eigenfunctions polynomial axial amplification and the existence of boundary layers. The resulting eigenvalues explicitly depend on the location of the boundaries, namely those of the baseflow disturbance and the duct exit, and are then validated by performing Direct Numerical Simulations. First, they successfully describe flow response to an initial disturbance with sidewall velocity injection break. Then, the simulated forced response to acoustics consists in vortical structures wihich discrete frequencies that are in good agreement with those of the eigenmodes. These structures are reflected into upstream pressure waves with identical frequencies. Finally, the PVS, which response to a compressible forcing such as the acoustic one is linear, is understood as the driving phenomenon of the Pressure Oscillations thanks to both numerical simulation and stability theory.