Several motor problems in ADHD learners are reported, including problems with balance, fine muscle control (Szatmari & Taylor; 1984; Havey & Reid, 2003) and motor planning (Piek et al., 1999; Pless & Corisson, 2000). It seems that overlapping conditions such as DAMP (which is a combination of ADHD and Developmental Coordination Disorder (DCD)) display greater connections with motor problems, than when a child displays only ADHD symptoms (Gillberg, 2003; Gibbs et al., 2007). There is also continuing controversy in the research literature as to whether ADHD is in fact remediable and what the most appropriate methods in this regard would be. Behavioural therapy at school and various forms of psychotherapy are reported to be the most popular forms of interventions complementary to medication. It also appears that motor exercise can stimulate the brain in various ways, resulting in improvement in learning and attention (Summerford, 2005). Motor therapy appears to be important, since many ADHD learners display motor difficulties. Motor control problems of learners with ADHD are also neglected during research. The objectives of this study were firstly to determine the nature and extent of coordination related neuro-motor and visual-motor integration deficits of an availability sample of six- to eight-year-old (N=95) learners diagnosed with ADHD in Brakpan, South Africa. A further objective was to determine whether treatment methods, including neuro-motor therapy, pharmacological agents and neuro biofeedback can indeed address neuro-motor problems and ADHD symptoms successfully. A further objective was to determine which of the various treatment programs, including neuro-motor therapy, pharmacological agents and brain conditioning intervention, will be the most effective for the treatment of six- to eight-year-old ADHD learners. The "Disruptive Behaviour Scale" checklist for ADHD (Bester, 2006) was used to identify learners with ADHD. The "Movement Assessment Battery for Learners 2" (MABC), and the “Quick Neurological Screening Test II" (QNST-II) were used to determine the learners’ motor skills, as well as neuro-motor progress. The "Beery Developmental Test of Visual-Motor Integration" (VMI-IV) was used to examine the learners' visual-motor integration (VMI), visual perception (VP) and motor coordination (MC). "Statistica for Windows 2012" was used for the analysis of the results. One-way Analysis of Variance, independent t-testing and co-variance analysis were used respectively to analyze data related to the abovementioned objectives. A p-value less than or equal to 0.05 was accepted as statistically significant, and effect sizes were calculated to determine the practical significance of the results (d≤0.8). The results of the study showed that the neuro-motor status of the selected six- to eight-year-old ADHD learners (N=95) that had been identified, using the Bester questionnaire, and analyzed by means of the MABC, QNST and VMI, was affected negatively by the condition. Fine motor and hand control skills of learners with ADHD were indeed found to be significantly weaker compared to learners without ADHD, and the fine motor skills of learners with DAMP showed impairment to a greater degree. Neurological and visual-motor integration do not appear to differ between learners with and without ADHD symptoms, although trends of weaker values and significant differences were found in the palm shape recognition, arm-leg extension (muscle tone) subscale and the stimulation of hand and cheek subscale in the ADHD and DAMP groups. For objective 2, the learners were divided into two groups (an ADHD intervention group (n=10) that was subjected to an neuro-motor intervention program of nine weeks, 37 minutes per session, twice a week, and compared to a non-control group consisting of non-ADHD learners (n=18)). When the pre-test differences between the groups are taken into account, it indicated that the ADHD group performed weaker than the control group in the QNST and MABC total, MABC percentile, ball skills and palm shape recognition subtest values, before starting the intervention, but that during the after-test no more differences were observed between the groups. This suggests that the intervention group showed improvement and that their average values draw closer to those of the control group, confirming that the intervention did exert an influence on the deficits that these ADHD learners experienced. The neuro-motor dysfunction of the group of learners with ADHD did not show a significant improvement, although non- significant trends of improvement that occurred in all variables may indeed be attributed to the effect of the intervention. A reduction in the ADHD symptoms and improved visual-motor integration in learners with ADHD were observed, suggesting that the severity of the symptoms of ADHD displayed by this group before the start of the intervention was significantly reduced. For objective 3, the learners (n=95) were divided into five groups (Sharper Brain group (n=25); neuro-motor intervention group (n=21); medication group (n=17); a group with no symptoms of ADHD (n=18), and an ADHD control group (n=14)). The Sharper Brain group showed practical significant lower values than the ADHD control group and the medication group in most of the MABC variables, from which can be deduced that neuro-biofeedback therapy will not improve motor problems. The results obtained in the visual-motor integration subtest showed that the neuro-motor intervention group performed significantly better than the ADHD control group, although the groups did not differ significantly. ADHD symptoms decreased significantly in all groups, most of all in the Sharper Brain group, from which can be deduced that the intervention has possibilities to improve focus and attention. A trend also occurred (p>0.05) that the neuro-motor intervention contributed more to improving visual-motor integration than the other intervention groups, while the medication intervention meaningfully addressed visual perception skills. However, from the results could not be determined whether one group performed better than another group, as no significant differences occurred consistently between groups. The neuro-biofeedback therapy, medication and neuro-motor intervention each had a achieved a unique improvement, and it is recommended that a combination of the various intervention methods should be used in the treatment of ADHD. In summary, the conclusion can be drawn that ADHD learners experience problems with skills related to attention, visual-motor integration and fine motor skills to a greater extent than non-ADHD learners, and that learners diagnosed with DAMP display more serious problems in this regard. The results showed that the various interventions have various treatment effects, but did not have a significant effect on the motor status of the ADHD learners. The conclusion may be drawn that there is no one single method of treatment for learners with ADHD symptoms, but that a combination of treatment methods should rather be implemented. From the study it is clear that ADHD does indeed affect learners negatively, but also that the exposure to focused intervention programs has a positive effect on their neuro-motor skills and ADHD symptoms. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2014

Les processus neuro-inflammatoires sont observés dans de nombreux troubles neurodégénératifs. Les cellules microgliales étant les principales cellules immunitaires du système nerveux central, plusieurs recherches ont été menées afin de déterminer des molécules possédant des propriétés anti-inflammatoires au niveau de ces cellules. Une famille de polyphénols, les stilbènes (des dérivés du resvératrol), présentent des activités anti-inflammatoires au niveau périphérique et central. Dans notre étude, nous avons premièrement évalué les propriétés anti-inflammatoires de 25 stilbènes en déterminant leur capacité à inhiber la libération de NO dans un modèle de cellules microgliales BV-2 activées par le LPS. Dix stilbènes inhibent significativement cette production avec des IC50 comprises entre 3,9 ± 0,7 et 23,4 ±1,0 µM. Parmi ces composés, 1 monomère (moracine M) et 2 tétramères du resvératrol (vitisines A et B) diminuent la synthèse d’iNOS, enzyme responsable à la libération de NO, au niveau transcriptionnel et traductionnel. Nous avons ensuite mis en évidence que la moracine M inhibe la phosphorylation d’ERK1/2 et JNK (deux MAPK) et d’Akt (la voie PI3K/Akt) dans des cellules BV-2 activées. Ces enzymes étant impliquées dans la signalisation de la réponse inflammatoire, elles induisent la production de plusieurs médiateurs inflammatoires. La moracine M inhibe significativement la production de certains d'entre eux (NO, TNF-α, IL-1β et PGE2). Ce stilbène attenue également la synthèse de la protéine de mPGEs-1 (enzyme impliquée à la production de PGE2). Ainsi, la moracine M pourrait être un candidat potentiel pour prévenir l’inflammation impliquée dans les maladies neurodégénératives. / Chronic neuro-inflammatory processes observed in many neurodegenerative disorders. Microglia are the main immune cells of the central nervous system. Many studies have been conducted to find molecules with anti-inflammatory properties in the central nervous system. A family of polyphénols, Stilbenoids (resveratrol derivatives), showed anti-inflammatory effects in peripheral and central levels.In this study, we have first evaluated anti-inflammatory effects of 25 stilbenes for their potential to inhibit NO release by LPS-activated BV-2 microglial cells. Ten stilbenes significantly reduced LPS-induced NO production with IC50 ranging from 3.9 ± 0.7 to 23.4 ±1.0 µM. Among these molecules 1 monomer (moracin M) and two tetramers (vitisins A and B) attenuated the expression of iNOS, a responsible enzyme for NO release on transcriptional and translational levels. Then, we have demonstrated that moracin M inhibits ERK1/2 and JNK phosphorylation of MAPK pathway and Akt phosphorylation of PI3K/Akt pathway, two signaling pathways involved in the inflammatory response in activated BV-2 cells. Indeed, the activation of these pathways leads to the production of several inflammatory mediators. We have shown that moracin M significantly inhibits the production of certain mediators such as NO, TNF-α, IL-1β and PGE2. This stilbene reduces the synthesis of mPGES-1 protein (an enzyme involved in the production of PGE2). In conclusion, we suggest that moracine M could be a potential candidate prevents the inflammation which involved in the progress of neurodegenerative diseases.

[pt] Esta tese investiga modelos híbridos neuro-fuzzy para aprendizado automático de ações efetuadas por agentes. O objetivo dos modelos é dotar um agente de inteligência, tornando-o capaz de, através da interação com o seu ambiente, adquirir e armazenar o conhecimento e raciocinar (inferir uma ação). O aprendizado desses modelos é realizado através de processo não-supervisionado denominado Aprendizado por Reforço (RL: Reinforcement Learning). Esta nova proposta de modelos neuro-fuzzy apresenta as seguintes características: aprendizado automático da estrutura do modelo; auto-ajuste dos parâmetros associados à estrutura; capacidade de aprender a ação a ser tomada quando o agente está em um determinado estado do ambiente; possibilidade de lidar com um número maior de entradas do que os sistemas neuro-fuzzy tradicionais; e geração de regras lingüísticas com hierarquia. O trabalho envolveu três etapas principais: levantamento bibliográfico e estudo de modelos de aprendizado; definição e implementação de dois novos modelos neuro-fuzzy hierárquicos baseados em RL; e estudo de casos. O levantamento bibliográfico e o estudo de modelos de aprendizado foi feito a partir dos modelos usados em agentes (com o objetivo de ampliar a ação autônoma) e em espaço de estados grande e/ou contínuo. A definição dos dois novos modelos neuro-fuzzy foi motivada pela importância de se estender a capacidade autônoma de agentes através do quesito inteligência, em particular a capacidade de aprendizado. Os modelos foram concebidos a partir do estudo das limitações existentes nos modelos atuais e das características desejáveis para sistemas de aprendizado baseados em RL, em particular quando aplicados a ambientes contínuos e/ou ambientes considerados de grande dimensão. Tais ambientes apresentam uma característica denominada curse of dimensionality que inviabiliza a aplicação direta de métodos tradicionais de RL. Assim sendo, a decisão de se usar uma metodologia de particionamento recursivo, já explorada com excelentes resultados em Souza (1999), que reduz significativamente as limitações dos sistemas neuro-fuzzy existentes, foi de fundamental importância para este trabalho. Optou-se pelos particionamentos BSP e Quadtree/Politree, gerando os dois modelos RL-NFHB (Reinforcement Learning - Neuro-Fuzzy Hierárquico BSP) e RL-NFHP (Reinforcement Learning - Neuro-Fuzzy Hierárquico Politree). Estes dois novos modelos são derivados dos modelos neuro-fuzzy hierárquicos NFHB e NFHQ (Souza, 1999) que utilizam aprendizado supervisionado. Com o uso desses métodos de particionamento, associados ao Reinforcement Learning, obteve-se uma nova classe de Sistemas Neuro-Fuzzy (SNF) que executam, além do aprendizado da estrutura, o aprendizado autônomo das ações a serem tomadas por um agente. Essas características representam um importante diferencial em relação aos sistemas de aprendizado de agentes inteligentes existentes. No estudo de casos, os dois modelos foram testados em 3 aplicações benckmark e uma aplicação em robótica. As aplicações benchmark são referentes a 3 problemas de sistemas de controle: o carro na montanha (mountain cart problem), estacionamento do carro (cart-centering problem) e o pêndulo invertido. A aplicação em robótica utilizou o modelo Khepera. A implementação dos modelos RL-NFHB e RL- NFHP foi feita em linguagem Java em microcomputadores com plataforma Windows 2000. Os testes efetuados demonstram que estes novos modelos se ajustam bem a problemas de sistemas de controle e robótica, apresentando boa generalização e gerando sua própria estrutura hierárquica de regras com interpretação lingüística. Além disso, o aprendizado automático do ambiente dota o agente de inteligência - (base de conhecimento, raciocínio e aprendizado), característica que aumenta a capacidade autônoma deste agente. A área de sistemas neuro-fuzzy hie / [en] This thesis investigates neuro-fuzzy hybrid models for automatic learning of actions taken by agents. The objective of these models is to provide an agent with intelligence, making it capable of acquiring and retaining knowledge and of reasoning (infer an action) by interacting with its environment. Learning in these models is performed by a non-supervised process, called Reinforcement Learning. These novel neuro-fuzzy models have the following characteristics: automatic learning of the model structure; auto-adjustment of parameters associated with the structure; capability of learning the action to be taken when the agent is on a given environment state; possibility of dealing with a larger number of inputs than those of traditional neuro-fuzzy systems; and the generation of hierarchical linguistic rules. This work comprised three main stages: bibliographic survey and study of learning models; definition and implementation of two new hierarchical neurofuzzy models based on Reinforcement Learning; and case studies. The bibliographic survey and the study of learning models considered learning models employed in agents (aiming to enhance the autonomous action) and in large and/or continuous state spaces. The definition of the two new neuro-fuzzy models was motivated by the importance of extending the autonomous capacity of agents through its intelligence, particularly the learning capacity. The models were conceived from the study of the existing limitations in current models, as well as the desirable characteristics for RL-based learning systems, particularly, when applied to continuous and/or high dimension environments. These environments present a characteristic called curse of dimensionality, which makes impracticable the direct application of the traditional RL- methods. Therefore, the decision of using a recursive partitioning methodology (already explored with excellent results in Souza, 1999), which significantly reduces the existing neuro-fuzzy systems limitations, was crucial to this work. The BSP (Binary Space Partitioning) and the Quadtree/Politree partitioning were then chosen, generating the RL-NFHB (Reinforcement Learning - Hierarchical Neuro- Fuzzy BSP) and RL-NFHP (Reinforcement Learning - Hierarchical Neuro-Fuzzy Politree) models. These two new models are derived from the hierarchical neuro-fuzzy models NFHB and NFHQ (Souza, 1999), which use supervised learning. By using these partitioning methods, together with the Reinforcement Learning methodology, a new class of Neuro-Fuzzy Systems (SNF) was obtained, which executes, in addition to structure learning, the autonomous learning of the actions to be taken by an agent. These characteristics represent an important differential when compared to the existing intelligent agents learning systems. In the case studies, the two models were tested in three benchmark applications and one application in robotics. The benchmark applications refer to 3 problems of control systems : the mountain cart problem, cart-centering problem, and the inverted pendulum. The application in robotics made use of the Khepera model. The RL-NFHB and RL-NFHP models were implemented using the Java language in Windows 2000 platform microcomputers. The experiments demonstrate that these new models are suitable for problems of control systems and robotics, presenting a good generalization and generating their own hierarchical structure of rules with linguistic interpretation. Moreover, the automatic environment learning endows the agent with intelligence (knowledge base, reasoning and learning). These are characteristics that increase the autonomous capacity of this agent. The hierarchical neuro-fuzzy systems field was also enhanced by the introduction of reinforcement learning, allowing the learning of hierarchical rules and actions to take place within the same process.

[pt] Desde sua formulação, no início da década de setenta, o conceito de grupo estratégico é objeto de pesquisas teóricas e empíricas que buscam confirmar sua existência, sua contribuição à avaliação da performance e à formação das estratégias das empresas. Este trabalho soma-se a estas pesquisas, utilizando os conceitos da Visão Resource- Based e a aplicação de ferramentas de inteligência computacional, neste caso as redes neurais e os sistemas de inferência fuzzy, com o objetivo de contribuir para a discussão deste tema na superação de suas limitações e dos novos desafios que o aumento da complexidade das arenas competitivas trouxeram para as pesquisas do gerenciamento estratégico. A Visão Resource-Based fornece a base teórica para o desenvolvimento dos construtos: grau de inimitabilidade e grau de imobilidade, resultantes da exploração estratégica dos recursos da empresa. Estes construtos são propostos como dimensões de avaliação da semelhança estratégica entre as empresas de uma arena competitiva. A inteligência computacional fornece os meios de extração de informações subjetivas, e presentes em ambientes complexos, através da simulação do aprendizado, percepção, evolução e adaptação do raciocínio humano. O resultado é a proposição de um modelo de avaliação da existência de grupos estratégicos, utilizando os construtos Grau de Inimitabilidade e Grau de Imobilidade, e Sistemas Neuro-fuzzy. Este modelo é aplicado ao setor de supermercados como teste de validação do mesmo. / [en] Since its has introduced, in the beginning of the decade of seventy, the concept of strategic groups is object of theoretical and empirical research that aims to confirm its existence, its contribution to performance evaluation and the formulation of the strategies of the firms. This text join these research, using the Resource-Based Views framework and soft computing, in this case neural networks and fuzzy inference systems, with aims at contributing for the discussion of this subject to overcome its limitations and the new challenges, resulting increasingly complexity and competitive environment, for the strategic management research. The Resource-Based View framework supplies the theoretical underpinnings to use the inimitability degree and immobility degree, resultants of the strategical exploration of the resources of the firms, as constructors to evaluate firm strategic similarity in a competitive environment. Soft computing is a tool to extract subjective data from complexity environments, simulating the ability for learning, perception, evolution and adaptation of human reasoning. The result of this research is the proposal of a model to identify strategic groups, applying the constructors Inimitability Degree and Immobility Degree, and Neuro-fuzzy Inference Systems. To validate the model, a test is performed to the supermarkets industry.

Several motor problems in ADHD learners are reported, including problems with balance, fine muscle control (Szatmari & Taylor; 1984; Havey & Reid, 2003) and motor planning (Piek et al., 1999; Pless & Corisson, 2000). It seems that overlapping conditions such as DAMP (which is a combination of ADHD and Developmental Coordination Disorder (DCD)) display greater connections with motor problems, than when a child displays only ADHD symptoms (Gillberg, 2003; Gibbs et al., 2007). There is also continuing controversy in the research literature as to whether ADHD is in fact remediable and what the most appropriate methods in this regard would be. Behavioural therapy at school and various forms of psychotherapy are reported to be the most popular forms of interventions complementary to medication. It also appears that motor exercise can stimulate the brain in various ways, resulting in improvement in learning and attention (Summerford, 2005). Motor therapy appears to be important, since many ADHD learners display motor difficulties. Motor control problems of learners with ADHD are also neglected during research. The objectives of this study were firstly to determine the nature and extent of coordination related neuro-motor and visual-motor integration deficits of an availability sample of six- to eight-year-old (N=95) learners diagnosed with ADHD in Brakpan, South Africa. A further objective was to determine whether treatment methods, including neuro-motor therapy, pharmacological agents and neuro biofeedback can indeed address neuro-motor problems and ADHD symptoms successfully. A further objective was to determine which of the various treatment programs, including neuro-motor therapy, pharmacological agents and brain conditioning intervention, will be the most effective for the treatment of six- to eight-year-old ADHD learners. The "Disruptive Behaviour Scale" checklist for ADHD (Bester, 2006) was used to identify learners with ADHD. The "Movement Assessment Battery for Learners 2" (MABC), and the “Quick Neurological Screening Test II" (QNST-II) were used to determine the learners’ motor skills, as well as neuro-motor progress. The "Beery Developmental Test of Visual-Motor Integration" (VMI-IV) was used to examine the learners' visual-motor integration (VMI), visual perception (VP) and motor coordination (MC). "Statistica for Windows 2012" was used for the analysis of the results. One-way Analysis of Variance, independent t-testing and co-variance analysis were used respectively to analyze data related to the abovementioned objectives. A p-value less than or equal to 0.05 was accepted as statistically significant, and effect sizes were calculated to determine the practical significance of the results (d≤0.8). The results of the study showed that the neuro-motor status of the selected six- to eight-year-old ADHD learners (N=95) that had been identified, using the Bester questionnaire, and analyzed by means of the MABC, QNST and VMI, was affected negatively by the condition. Fine motor and hand control skills of learners with ADHD were indeed found to be significantly weaker compared to learners without ADHD, and the fine motor skills of learners with DAMP showed impairment to a greater degree. Neurological and visual-motor integration do not appear to differ between learners with and without ADHD symptoms, although trends of weaker values and significant differences were found in the palm shape recognition, arm-leg extension (muscle tone) subscale and the stimulation of hand and cheek subscale in the ADHD and DAMP groups. For objective 2, the learners were divided into two groups (an ADHD intervention group (n=10) that was subjected to an neuro-motor intervention program of nine weeks, 37 minutes per session, twice a week, and compared to a non-control group consisting of non-ADHD learners (n=18)). When the pre-test differences between the groups are taken into account, it indicated that the ADHD group performed weaker than the control group in the QNST and MABC total, MABC percentile, ball skills and palm shape recognition subtest values, before starting the intervention, but that during the after-test no more differences were observed between the groups. This suggests that the intervention group showed improvement and that their average values draw closer to those of the control group, confirming that the intervention did exert an influence on the deficits that these ADHD learners experienced. The neuro-motor dysfunction of the group of learners with ADHD did not show a significant improvement, although non- significant trends of improvement that occurred in all variables may indeed be attributed to the effect of the intervention. A reduction in the ADHD symptoms and improved visual-motor integration in learners with ADHD were observed, suggesting that the severity of the symptoms of ADHD displayed by this group before the start of the intervention was significantly reduced. For objective 3, the learners (n=95) were divided into five groups (Sharper Brain group (n=25); neuro-motor intervention group (n=21); medication group (n=17); a group with no symptoms of ADHD (n=18), and an ADHD control group (n=14)). The Sharper Brain group showed practical significant lower values than the ADHD control group and the medication group in most of the MABC variables, from which can be deduced that neuro-biofeedback therapy will not improve motor problems. The results obtained in the visual-motor integration subtest showed that the neuro-motor intervention group performed significantly better than the ADHD control group, although the groups did not differ significantly. ADHD symptoms decreased significantly in all groups, most of all in the Sharper Brain group, from which can be deduced that the intervention has possibilities to improve focus and attention. A trend also occurred (p>0.05) that the neuro-motor intervention contributed more to improving visual-motor integration than the other intervention groups, while the medication intervention meaningfully addressed visual perception skills. However, from the results could not be determined whether one group performed better than another group, as no significant differences occurred consistently between groups. The neuro-biofeedback therapy, medication and neuro-motor intervention each had a achieved a unique improvement, and it is recommended that a combination of the various intervention methods should be used in the treatment of ADHD. In summary, the conclusion can be drawn that ADHD learners experience problems with skills related to attention, visual-motor integration and fine motor skills to a greater extent than non-ADHD learners, and that learners diagnosed with DAMP display more serious problems in this regard. The results showed that the various interventions have various treatment effects, but did not have a significant effect on the motor status of the ADHD learners. The conclusion may be drawn that there is no one single method of treatment for learners with ADHD symptoms, but that a combination of treatment methods should rather be implemented. From the study it is clear that ADHD does indeed affect learners negatively, but also that the exposure to focused intervention programs has a positive effect on their neuro-motor skills and ADHD symptoms. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2014

L'IRM de diffusion (IRMd) est une modalité d'imagerie médicale qui suscite un intérêt croissant dans la recherche en neuro-imagerie. Elle permet d'apporter in vivo des informations nouvelles sur les micro-structures locales des tissus. En chaque point d'une acquisition d'IRMd, la distribution des directions de diffusion des molécules d'eau est modélisée par un tenseur de diffusion. La nature multivariée de ces images requiert la conception de nouvelles méthodes de traitement adaptées. Le contexte de cette thèse est l'analyse automatique de changements longitudinaux intra-patient avec pour application le suivi de pathologies neuro-dégénératives. Notre recherche a ainsi porté sur le développement de nouveaux modèles et tests statistiques permettant la détection automatique de changements sur des séquences temporelles d'images de diffusion. Cette thèse a ainsi permis une meilleure prise en compte de la nature tensorielle des modèles d'ordre 2 (tests statistiques sur des matrices définies positives), une extension vers des modèles d'ordre supérieur et une gestion plus fine des voisinages sur lesquels les tests sont menés, avec en particulier la conception de tests statistiques sur des faisceaux de fibres. / Diffusion MRI is a new medical imaging modality of great interest in neuroimaging research. This modality enables the characterization in vivo of local micro-structures. Tensors have commonly been used to model the diffusivity profile at each voxel. This multivariate data set requires the design of new dedicated image processing techniques. The context of this thesis is the automatic analysis of intra-patient longitudinal changes with application to the follow-up of neuro-degenerative pathologies. Our research focused on the development of new models and statistical tests for the automatic detection of changes in temporal sequences of diffusion images. Thereby, this thesis led to a better modeling of second order tensors (statistical tests on positive definite matrices), to an extension to higher-order models, and to the definition of refined neighborhoods on which tests are conducted, in particular the design of statistical tests on fiber bundles.

Les douleurs oculaires aiguës et chroniques sont parmi les plus invalidantes et les plus difficiles à traiter. Elles touchent plus particulièrement la cornée, tissu le plus innervé et le plus sensible du corps humain. Cette riche innervation provient des neurones sensoriels primaires localisés dans le ganglion trijumeau (GT) qui transmettent directement l'information douloureuse au niveau du complexe sensitif du trijumeau (CST). Cependant, les mécanismes physiopathologiques de la douleur oculaire de nature neurogène et/ou inflammatoire demeurent de nos jours encore mal connus. Un approfondissement des connaissances fondamentales sur l'anatomie du système nociceptif cornéen mais aussi sur les mécanismes cellulaires et moléculaires impliqués dans l'initiation et la chronicisation de la douleur oculaire, sont donc indispensables à l'amélioration des thérapies actuelles. Dès lors, les travaux de cette thèse se sont donc orientés sur deux axes principaux ; 1) approfondir les connaissances neuroanatomiques du système nociceptif cornéen en établissant la première cartographie tridimensionnelle des neurones cornéens au sein du GT ; 2) étudier les conséquences neuro-inflammatoires des voies trigéminées cornéennes (cornée, GT et CST) dans un modèle murin de douleur oculaire induit par des instillations chroniques de chlorure de benzalkonium (conservateur neurotoxique). Dans l'ensemble, nos travaux expérimentaux montrent qu'une lésion cornéenne chez la souris induit une neuro-inflammation qui se propage de la périphérie jusqu'au système nerveux central, et offrent de nouvelles perspectives thérapeutiques pour les patients atteints de douleurs oculaires aiguës ou chroniques. / Acute and chronic eye pain are among the most debilitating and difficult to treat. They particularly affect the cornea, the most innervated and most sensitive tissue of the human body. Corneal innervation comes from primary sensory neurons localized in the trigeminal ganglion (TG) that directly transmit pain information to the trigeminal sensory complex (TSC). However, pathophysiological mechanisms of ocular pain with neurogenic and /or inflammatory type remain poorly understood. Deeper fundamental knowledge about the anatomy of the corneal nociceptive system and the cellular and molecular mechanisms involved in the initiation and chronicity of eye pain, are essential to improving current therapies. Therefore, the work of this thesis are focused on two main topic: 1) expand our current knowledge about the neuroanatomy of the corneal nociceptive system by establishing the first three-dimensional mapping of corneal neurons within the TG; 2) study the neuro-inflammatory consequences in the corneal trigeminal pathways (cornea, TG and TSC) in a murine model of ocular pain induced by chronic instillations of benzalkonium chloride (neurotoxic preservative). Overall, our experimental work reveals that a corneal lesion in mice induces neuroinflammation that spreads from the periphery to the central nervous system, and offer new therapeutic opportunities for patients with acute or chronic eye pain.

El presente plan de negocio muestra la viabilidad de la Implementación de un Programa de Bienestar nutricional para la pequeña y mediana empresa de la Provincia Constitucional del Callao, donde las empresas que tomen el servicio brindarán a sus trabajadores la posibilidad de acceder a herramientas que les permitirán mejorar su salud, así también a la organización en el incremento de su productividad. Para analizar la viabilidad de su ejecución se llevó a cabo una investigación de mercado que evidencio en nuestro segmento un mayor número de empresas en el rubro de manufactura, transporte y almacenamiento, así también nos muestra el interés por mejorar la alimentación de sus trabajadores pues consideran su influencia con la productividad. La empresa Salud Laboral SRL brindará el servicio de “Programa de Bienestar Nutricional en las pequeñas y medianas empresas de la Provincia Constitucional del Callao”, el mismo que consiste en consulta nutricional, talleres educativos aplicando la técnica de Programación Neuro Lingüística(PNL) y la Inspección a lugares de expendio de alimentos. El servicio estará a cargo de nutricionistas y psicólogos; quienes adaptaran la metodología de acuerdo al requerimiento de las empresas contratantes y del presupuesto que los mismos dispongan, realizando las actividades en sus instalaciones. Con ello aportaremos en la mejorar de la salud de los beneficiarios desarrollando un enfoque de fidelización, productividad y seguridad. Finalmente, el análisis financiero encontró una tasa interna de retorno y un valor actual neto favorable lo que permite recomendar la inversión en este proyecto. / This business plan shows the viability of implementing a Nutritional Wellness Program for small and medium enterprises in the Constitutional Province of Callao. The companies that take the service will offer their workers the possibility to access tools that will allow them to improve their health, as well as the organization in increasing their productivity. To analyze the viability we made a market investigation that evidenced in our segment a greater number of companies in the field of manufacturing, transport and storage, as well as the interest to improve the food supply of its workers because they consider it is importaht to improve the productivity. The company Salud Laboral SRL will offer the service of "Nutritional Wellness Program” in small and medium enterprises of the Constitutional Province of Callao, this program consists of nutritional assesment, educational workshops applying the Neuro Linguistic Programming Technique (NLP) and the Inspection of places that sell food. The service will be in charge of nutritionists and psychologists who will adapt the methodology according to the requirements of the contracting companies and the budget that they have, carrying out the activities in their facilities. With this we will contribute in improving the health of the beneficiaries by developing a loyalty, productivity and safety approach. Finally, the financial analysis found an internal rate of return and a net present value favorable which allows us to recommend the investment in this Project. / Tesis

The thesis deals with the evaluation and training of cognitive-visual functions of elite athletes using the NeuroTracker computer program. The theoretical part pursues collecting of recent studies and literature, concerning predominantly visual perception and its connection with cognitive abilities and movement. It focuses mainly on sportsmen and evaluation of their visual functions. Furthemore it introduces the concept of neurovisual training and its possible application in other clinical fields. Methodology: The NeuroTracker program evaluates reaction abilities, visual memory, spatial imagination and other components of cognitive and visual functions. The output of this evaluation is a numerical value before and after training and calculated percentage improvement. This change was measured in a group of 64 athletes of various sports. The thesis also includes case reports of two athletes who underwent a general optometric examination, which was complemented by further visual training. Results: We have showed statistically that after a series of trainings on the NeuroTracker, there is an overall improvement of the measured parameters. Moreover we have shown that the number of performed trainings moderately correlates with the resulting improvement. Each sport correlates in a different way however....

[pt] Esta tese consiste na investigação e no desenvolvimento de estratégias de coordenação inteligente que possam ser integradas a modelos neuro-fuzzy hierárquicos para sistemas de múltiplos agentes em ambientes complexos. Em ambientes dinâmicos ou complexos a organização dos agentes deve se adaptar a mudanças nos objetivos do sistema, na disponibilidade de recursos, nos relacionamentos entre os agentes, e assim por diante. Esta flexibilidade é um problema chave nos sistemas multiagente. O objetivo principal dos modelos propostos é fazer com que múltiplos agentes interajam de forma inteligente entre si em sistemas complexos. Neste trabalho foram desenvolvidos dois novos modelos inteligentes neuro-fuzzy hierárquicos com mecanismo de coordenação para sistemas multiagentes, a saber: modelo Neuro-Fuzzy Hierárquico com Aprendizado por Reforço com mecanismo de coordenação Market-Driven (RL-NFHP-MA-MD); e o Modelo Neuro-Fuzzy Hierárquico com Aprendizado por Reforço com modelo de coordenação por grafos (RL-NFHP-MA-CG). A inclusão de modelos de coordenação ao modelo Neuro-Fuzzy Hierárquicos com Aprendizado por Reforço (RL-NHFP-MA) foi motivada principalmente pela importância de otimizar o desempenho do trabalho em conjunto dos agentes, melhorando os resultados do modelo e visando aplicações mais complexas. Os modelos foram concebidos a partir do estudo das limitações existentes nos modelos atuais e das características desejáveis para sistemas de aprendizado baseados em RL, em particular quando aplicados a ambientes contínuos e/ou ambientes considerados de grande dimensão. Os modelos desenvolvidos foram testados através de basicamente dois estudos de caso: a aplicação benchmark do jogo da presa-predador (Pursuit- Game) e Futebol de robôs (simulado e com agentes robóticos). Os resultados obtidos tanto no jogo da presa-predador quanto no futebol de robô através dos novos modelos RL-NFHP-MA-MD e RL-NFHP-MA-CG para múltiplos agentes se mostraram bastante promissores. Os testes demonstraram que o novo sistema mostrou capacidade de coordenar as ações entre agentes com uma velocidade de convergência quase 30 por cento maior que a versão original. Os resultados de futebol de robô foram obtidos com o modelo RL-NFHP-MA-MD e o modelo RL-NFHP-MA-CG, os resultados são bons em jogos completos como em jogadas específicas, ganhando de times desenvolvidos com outros modelos similares. / [en] This thesis is the research and development of intelligent coordination strategies that can be integrated into models for hierarchical neuro-fuzzy systems of multiple agents in complex environments. In dynamic environments or complex organization of agents must adapt to changes in the objectives of the system, availability of resources, relationships between agents, and so on. This flexibility is a key problem in multiagent systems. The main objective of the proposed models is to make multiple agents interact intelligently with each other in complex systems. In this work we developed two new intelligent neuro-fuzzy models with hierarchical coordination mechanism for multi-agent systems, namely Neuro-Fuzzy Model with Hierarchical Reinforcement Learning with coordination mechanism Market-Driven (RL-NFHP-MA-MD), and Neuro-Fuzzy model with Hierarchical Reinforcement Learning with coordination model for graphs (RL-NFHP-MA-CG). The inclusion of coordination models to model with Neuro-Fuzzy Hierarchical Reinforcement Learning (RL-NHFP-MA) was primarily motivated by the importance of optimizing the performance of the work in all players, improving the model results and targeting more complex applications. The models were designed based on the study of existing limitations in current models and desirable features for learning systems based RL, in particular when applied to continuous environments and/or environments considered large. The developed models were tested primarily through two case studies: application benchmark game of predator-prey ( Pursuit-Game) and Soccer robots (simulated and robotic agents). The results obtained both in the game of predator-prey as in soccer robot through new models RL-NFHP-MA-MD and RL-NFHP-MA-CG for multiple agents proved promising. The tests showed that the new system showed ability to coordinate actions among agents with a convergence rate nearly 30 percent higher than the original version. Results soccer robot were obtained with model RL-NFHP-MA-MD–NFHP-RL and model-CG-MA, the results are good in games played in full as specific winning teams developed with other similar models.