Cholinergic enhancement of perceptual learning : behavioral, physiological, and neuro-pharmacological study in the rat primary visual cortex

Les cortices sensoriels sont des régions cérébrales essentielles pour la perception. En particulier, le cortex visuel traite l’information visuelle en provenance de la rétine qui transite par le thalamus. Les neurones sont les unités fonctionnelles qui transforment l'information sensorielle en signaux électriques, la transfèrent vers le cortex et l'intègrent. Les neurones du cortex visuel sont spécialisés et analysent différents aspects des stimuli visuels. La force des connections entre les neurones peut être modulée par la persistance de l'activité pré-synaptique et induit une augmentation ou une diminution du signal post-synaptique à long terme. Ces modifications de la connectivité synaptique peuvent induire la réorganisation de la carte corticale, c’est à dire la représentation de ce stimulus et la puissance de son traitement cortical. Cette réorganisation est connue sous le nom de plasticité corticale. Elle est particulièrement active durant la période de développement, mais elle s’observe aussi chez l’adulte, par exemple durant l’apprentissage. Le neurotransmetteur acétylcholine (ACh) est impliqué dans de nombreuses fonctions cognitives telles que l’apprentissage ou l’attention et il est important pour la plasticité corticale. En particulier, les récepteurs nicotiniques et muscariniques du sous-type M1 et M2 sont les récepteurs cholinergiques impliqués dans l’induction de la plasticité corticale. L’objectif principal de la présente thèse est de déterminer les mécanismes de plasticité corticale induits par la stimulation du système cholinergique au niveau du télencéphale basal et de définir les effets sur l’amélioration de la perception sensorielle. Afin d’induire la plasticité corticale, j’ai jumelé des stimulations visuelles à des injections intracorticales d’agoniste cholinergique (carbachol) ou à une stimulation du télencéphale basal (neurones cholinergiques qui innervent le cortex visuel primaire). J'ai analysé les potentiels évoqués visuels (PEVs) dans le cortex visuel primaire des rats pendant 4 à 8 heures après le couplage. Afin de préciser l’action de l’ACh sur l’activité des PEVs dans V1, j’ai injecté individuellement l’antagoniste des récepteurs muscariniques, nicotiniques, α7 ou NMDA avant l’infusion de carbachol. La stimulation du système cholinergique jumelée avec une stimulation visuelle augmente l’amplitude des PEVs durant plus de 8h. Le blocage des récepteurs muscarinique, nicotinique et NMDA abolit complètement cette amélioration, tandis que l’inhibition des récepteurs α7 a induit une augmentation instantanée des PEVs. Ces résultats suggèrent que l'ACh facilite à long terme la réponse aux stimuli visuels et que cette facilitation implique les récepteurs nicotiniques, muscariniques et une interaction avec les récepteur NMDA dans le cortex visuel. Ces mécanismes sont semblables à la potentiation à long-terme, évènement physiologique lié à l’apprentissage. L’étape suivante était d’évaluer si l’effet de l’amplification cholinergique de l’entrée de l’information visuelle résultait non seulement en une modification de l’activité corticale mais aussi de la perception visuelle. J’ai donc mesuré l’amélioration de l’acuité visuelle de rats adultes éveillés exposés durant 10 minutes par jour pendant deux semaines à un stimulus visuel de type «réseau sinusoïdal» couplé à une stimulation électrique du télencéphale basal. L’acuité visuelle a été mesurée avant et après le couplage des stimulations visuelle et cholinergique à l’aide d’une tâche de discrimination visuelle. L’acuité visuelle du rat pour le stimulus d’entrainement a été augmentée après la période d’entrainement. L’augmentation de l’acuité visuelle n’a pas été observée lorsque la stimulation visuelle seule ou celle du télencéphale basal seul, ni lorsque les fibres cholinergiques ont été lésées avant la stimulation visuelle. Une augmentation à long terme de la réactivité corticale du cortex visuel primaire des neurones pyramidaux et des interneurones GABAergiques a été montrée par l’immunoréactivité au c-Fos. Ainsi, lorsque couplé à un entrainement visuel, le système cholinergique améliore les performances visuelles pour l’orientation et ce probablement par l’optimisation du processus d’attention et de plasticité corticale dans l’aire V1. Afin d’étudier les mécanismes pharmacologiques impliqués dans l’amélioration de la perception visuelle, j’ai comparé les PEVs avant et après le couplage de la stimulation visuelle/cholinergique en présence d’agonistes/antagonistes sélectifs. Les injections intracorticales des différents agents pharmacologiques pendant le couplage ont montré que les récepteurs nicotiniques et M1 muscariniques amplifient la réponse corticale tandis que les récepteurs M2 muscariniques inhibent les neurones GABAergiques induisant un effet excitateur. L’infusion d’antagoniste du GABA corrobore l’hypothèse que le système inhibiteur est essentiel pour induire la plasticité corticale. Ces résultats démontrent que l’entrainement visuel jumelé avec la stimulation cholinergique améliore la plasticité corticale et qu’elle est contrôlée par les récepteurs nicotinique et muscariniques M1 et M2. Mes résultats suggèrent que le système cholinergique est un système neuromodulateur qui peut améliorer la perception sensorielle lors d’un apprentissage perceptuel. Les mécanismes d’amélioration perceptuelle induits par l’acétylcholine sont liés aux processus d’attention, de potentialisation à long-terme et de modulation de la balance d’influx excitateur/inhibiteur. En particulier, le couplage de l’activité cholinergique avec une stimulation visuelle augmente le ratio de signal / bruit et ainsi la détection de cibles. L’augmentation de la concentration cholinergique corticale potentialise l’afférence thalamocorticale, ce qui facilite le traitement d’un nouveau stimulus et diminue la signalisation cortico-corticale minimisant ainsi la modulation latérale. Ceci est contrôlé par différents sous-types de récepteurs cholinergiques situés sur les neurones GABAergiques ou glutamatergiques des différentes couches corticales. La présente thèse montre qu’une stimulation électrique dans le télencéphale basal a un effet similaire à l’infusion d’agoniste cholinergique et qu’un couplage de stimulations visuelle et cholinergique induit la plasticité corticale. Ce jumelage répété de stimulations visuelle/cholinergique augmente la capacité de discrimination visuelle et améliore la perception. Cette amélioration est corrélée à une amplification de l’activité neuronale démontrée par immunocytochimie du c-Fos. L’immunocytochimie montre aussi une différence entre l’activité des neurones glutamatergiques et GABAergiques dans les différentes couches corticales. L’injection pharmacologique pendant la stimulation visuelle/cholinergique suggère que les récepteurs nicotiniques, muscariniques M1 peuvent amplifier la réponse excitatrice tandis que les récepteurs M2 contrôlent l’activation GABAergique. Ainsi, le système cholinergique activé au cours du processus visuel induit des mécanismes de plasticité corticale et peut ainsi améliorer la capacité perceptive. De meilleures connaissances sur ces actions ouvrent la possibilité d’accélérer la restauration des fonctions visuelles lors d’un déficit ou d’amplifier la fonction cognitive.

Performance Improvement of Fuzzy and Neuro Fuzzy Systems: Prediction of Learning Disabilities in School-age Children

Learning Disability (LD) is a classification including several disorders in which a child has difficulty in learning in a typical manner, usually caused by an unknown factor or factors. LD affects about 15% of children enrolled in schools. The prediction of learning disability is a complicated task since the identification of LD from diverse features or signs is a complicated problem. There is no cure for learning disabilities and they are life-long. The problems of children with specific learning disabilities have been a cause of concern to parents and teachers for some time. The aim of this paper is to develop a new algorithm for imputing missing values and to determine the significance of the missing value imputation method and dimensionality reduction method in the performance of fuzzy and neuro fuzzy classifiers with specific emphasis on prediction of learning disabilities in school age children. In the basic assessment method for prediction of LD, checklists are generally used and the data cases thus collected fully depends on the mood of children and may have also contain redundant as well as missing values. Therefore, in this study, we are proposing a new algorithm, viz. the correlation based new algorithm for imputing the missing values and Principal Component Analysis (PCA) for reducing the irrelevant attributes. After the study, it is found that, the preprocessing methods applied by us improves the quality of data and thereby increases the accuracy of the classifiers. The system is implemented in Math works Software Mat Lab 7.10. The results obtained from this study have illustrated that the developed missing value imputation method is very good contribution in prediction system and is capable of improving the performance of a classifier.

Evaluation of Somaclonal Variation in Callus Cultures of Jatropha curcas Maintained on Different Hormonal Combinations Using RAPD Markers

Random genetic changes generated during in vitro culture are not desirable for plant micropropagation and genetic transformation. RAPD markers were used to detect the variation in leaf disc callus cultures of Jatropha curcas, maintained in Murashige and Skoog (MS) medium with different auxin and cytokinin combinations. In total 41 scorable bands were produced with 11 primers. Out of 41 bands, 37 were polymorphic (91.12%). The average number of polymorphic bands was 3.36 per primer. The highest similarity (0.82) with mother plant was seen in callus maintained on MS with hormonal combination Indole butyric acid - 0.4mg/l+ N6-benzyladenine purine - 4.0 mg/l. The callus grown on MS with hormonal combinations IBA- 0.4mg/l+ BAP- 2.0mg/l, IBA- 0.4mg/l+ BAP- 2.5mg/l and IBA- 0.6 mg/l+ BAP- 2.0 mg/l also showed similarity with the mother plant. Callus maintained on MS with hormonal combination IBA- 0.2mg/l+ BAP- 2.0 mg/l was found to show least similarity (0.53) with mother plant

Factores neuro-psicolingu??sticos y estrategias cognitivas implicadas en el aprendizaje de la lectura y programa de entrenamiento

Hacer una revisi??n de investigaciones directamente relacionadas con el tema propuesto. Demostrar emp??ricamente el peso relativo que poseen en el aprendizaje inicial de la lectura unos factores de naturaleza neuro-psicoling????stica, tradicionalmente considerados como madurativos, pero entendidos por los autores como competencias b??sicas para el aprendizaje. Demostrar experimentalmente la eficacia de un programa de entrenamiento, consistente en la aplicaci??n de una serie de tareas psicomotrices, psicoling????sticas y cognitivas, tendentes a modificar el ritmo de adquisici??n de tales competencias b??sicas en un grupo de ni??os de bajo nivel y, en consecuencia, a mejorar su aprendizaje de la lectura, mediante la puesta en pr??ctica de un modelo did??ctico propio. El universo de la investigaci??n hace referencia a ni??os entre 4 a??os y medio y 6 a??os, ubicados en ??ltimo curso de la ense??anza infantil, sin evidencia emp??rica de problema cerebral ni de retraso mental. La muestra real del primer dise??o la componen 348 ni??os de ambos sexos, de Zaragoza, Valladolid, Vigo y Baeza. La muestra del segundo dise??o fue la siguiente: se seleccionaron los 15 ni??os de puntuaciones m??s bajas de los 130 que formaban parte de la muestra de Zaragoza, para formar el grupo experimental. Los 15 ni??os del grupo de control fueron seleccionados en 5 aulas de Valladolid y Vigo: los 3 de cada una de esas aulas con puntuaciones m??s bajas en la bater??a diagn??stica aplicada. Estructura dividida en 3 partes. El n??cleo b??sico de las 2 primeras partes es una amplia revisi??n de investigaciones directamente relacionadas con la vasta y compleja problem??tica de los procesos de la pedagog??a del lenguaje escrito. En la parte tercera se presentan las bases t??cnico-pr??cticas de un modelo did??ctico propio, publicado hace unos cuantos a??os y actualizado para esta obra, como asimismo la validaci??n emp??rica y experimental de dicho modelo. Para llevar a cabo esa validaci??n el autor se ha valido predominantemente de una metodolog??a cuantitativa pero tambi??n se ha apoyado en datos cualitativos obtenidos a trav??s de un proceso de observaci??n sistem??tica. Muchas de las experiencias pedag??gicas que se autodenominan 'ense??anza temprana de la lectura' no son tales, pues dichos resultados demuestran que a los 4 a??os un ni??o normal est?? en condiciones de acceder al lenguaje escrito si se le facilitan los medios y se respetan los distintos momentos evolutivos. Es necesaria una investigaci??n m??s abundante acerca de las caracter??sticas de los textos empleados en la ense??anza de la lectura, tomando como referencia las distintas gram??ticas textuales, los modelos cognitivos del aprendizaje de la lectura y empleando pruebas de evaluaci??n de la comprensi??n lectora con suficiente validez de constructo y emp??rica, como as??mismo f??rmulas de lecturabilidad textual m??s complejas.

Sabes? Juntos aprendemos melhor : a atitude dos docentes face à inclusão de alunos com distúrbio hiperativo com défice de atenção

A inclusão de alunos com Necessidades Educativas Especiais, mais propriamente com Distúrbio Hiperativo e Défice de Atenção em turmas regulares é sempre um tema bastante delicado para os professores. São, contudo, amplamente conhecidas as vantagens da sua inclusão em turmas dessa natureza. Um modelo educacional que contemple esta mesma inclusão será, na nossa ótica, um modelo que tende a ter sucesso para os referidos alunos. Neste sentido, saber a opinião dos professores referente ao processo de inclusão de alunos com DHDA foi o grande objetivo para a nossa investigação. A amostra foi constituída por 50 professores dos diferentes níveis de ensino e pertencentes a três escolas do Agrupamento de Escolas de Caneças. Utilizámos um questionário como instrumento para aferir os dados e concluímos, neste estudo que: - a maior parte dos inquiridos estão familiarizados com o conceito de DHDA; - existe uma certa unanimidade a favor da inclusão dos alunos com DHDA, por parte dos professores; - a experiência profissional interfere diretamente na forma de os professores lidarem com a inclusão de alunos com DHDA nas suas turmas. Sabemos, que há ainda um longo caminho a percorrer para que o processo de inclusão dos alunos seja uma realidade. Uma escola que proporcione igualdade de oportunidades e que não discrimine quem é diferente, é uma escola inclusiva.

Intervenção Farmacêutica na Contraceção Hormonal e de Emergência

O acesso aos métodos contracetivos hormonais regulares e de emergência configura para as mulheres a possibilidade de controlar a sua natalidade com elevada eficácia e segurança. A contraceção de emergência deve ser encarada como um método de recurso, a um método principal de contraceção. A sua disponibilidade representa um valioso recurso para as mulheres, ao permitir efetuar uma contraceção com elevado grau de eficácia e segurança após o coito. Devido ao aumento do consumo de contracetivos de emergência em Portugal, associado à possibilidade em adquiri-los sem intervenção farmacêutica, torna-se necessário perceber o perfil de consumo da contraceção de emergência. O farmacêutico devido à sua proximidade geográfica e permanente disponibilidade para com a população que serve, aliado ás suas competências na área do medicamento, assume cada vez mais uma importância crescente ao nível da contraceção hormonal. O recurso à contraceção de emergência representa em grande parte dos casos uma falha contracetiva ou a não utilização de métodos contracetivos durante o coito. O farmacêutico ao estar diretamente envolvido na dispensa de ambos os métodos tem a capacidade de com a sua intervenção melhorar as praticas contracetivas entre as mulheres portuguesas e contribuir para a utilização racional de medicamentos. Os objetivos do trabalho monográfico foram: efetuar uma revisão sobre métodos contracetivos hormonais incluindo os de emergência e respetiva intervenção farmacêutica em Portugal. Analisar o consumo e utilização da contraceção de emergência em Portugal. Neste contexto o trabalho desenvolvido consistiu numa revisão sobre os principais métodos contracetivos hormonais e de emergência. Realizou-se uma análise entre o consumo de contracetivos de emergência e a interrupção voluntaria da gravidez na tentativa de estabelecer uma relação entre ambos. Explorou-se a ideia da inclusão do farmacêutico na consulta de planeamento familiar e outros serviços em que este poderia representar uma mais valia para a população. Sugeriu-se uma intervenção ativa do farmacêutico em Portugal, com vista a promover a melhor utilização dos métodos contracetivos à disposição das mulheres. Relativamente à metodologia utilizada esta consistiu numa pesquisa bibliográfica com recurso ao motor de busca pubmed. Foram ainda realizados contactos com profissionais de saúde responsáveis pelo planeamento familiar, farmacêuticos comunitários, hospitalares, Infarmed, Ordem dos Farmacêuticos e suas homologas internacionais e industria farmacêutica, de modo a obter informações sobre a disponibilidade, consumo e utilização de contracetivos hormonais incluindo os de emergência. Concluiu-se que a contraceção hormonal oral é a forma de eleição entre as mulheres portuguesas, sendo por isso um ponto onde o farmacêutico comunitário deve estar particularmente atualizado. O aumento no consumo de contracetivos de emergência em 2010 sugere a dispensa sem intervenção farmacêutica. Não é possível estabelecer uma relação entre o consumo de contracetivos de emergência e a interrupção voluntaria da gravidez. A intervenção farmacêutica tem o potencial para melhorar a utilização dos métodos contracetivos entre as mulheres portuguesas.

Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance

Emerging evidence suggests that dietary-derived flavonoids have the potential to improve human memory and neuro-cognitive performance via their ability to protect vulnerable neurons, enhance existing neuronal function and stimulate neuronal regeneration. Long-term potentiation (LTP) is widely considered to be one of the major mechanisms underlying memory acquisition, consolidation and storage in the brain and is known to be controlled at the molecular level by the activation of a number of neuronal signalling pathways. These pathways include the phosphatidylinositol-3 kinase/protein kinase B/Akt (Akt), protein kinase C, protein kinase A, Ca-calmodulin kinase and mitogen-activated protein kinase pathways. Growing evidence suggests that flavonoids exert effects on LTP, and consequently memory and cognitive performance, through their interactions with these signalling pathways. Of particular interest is the ability of flavonoids to activate the extracellular signal-regulated kinase and the Akt signalling pathways leading to the activation of the cAMP-response element-binding protein, a transcription factor responsible for increasing the expression of a number of neurotrophins important in LTP and long-term memory. One such neurotrophin is brain-derived neurotrophic factor, which is known to be crucial in controlling synapse growth, in promoting an increase in dendritic spine density and in enhancing synaptic receptor density. The present review explores the potential of flavonoids and their metabolite forms to promote memory and learning through their interactions with neuronal signalling pathways pivotal in controlling LTP and memory in human subjects.

Reach & grasp therapy: Design and control of a 9-DOF robotic neuro-rehabilitation system

This paper presents the Gentle/G integrated system for reach & grasp therapy retraining following brain injury. The design, control and integration of an experimental grasp assistance unit is described for use in robot assisted stroke rehabilitation. The grasp assist unit is intended to work with the hardware and software of the Gentle/S robot although the hardware could be adapted to other rehabilitation applications. When used with the Gentle/S robot a total of 6 active and 3 passive degrees of freedom are available to provide active, active assist or passive grasp retraining in combination with reaching movements in a reach-grasp-transfer-release sequence.

Design of a minimum variance multiple input-multiple output neuro self-tuning proportional-integral-derivative controller for non-linear dynamic systems

In this study a minimum variance neuro self-tuning proportional-integral-derivative (PID) controller is designed for complex multiple input-multiple output (MIMO) dynamic systems. An approximation model is constructed, which consists of two functional blocks. The first block uses a linear submodel to approximate dominant system dynamics around a selected number of operating points. The second block is used as an error agent, implemented by a neural network, to accommodate the inaccuracy possibly introduced by the linear submodel approximation, various complexities/uncertainties, and complicated coupling effects frequently exhibited in non-linear MIMO dynamic systems. With the proposed model structure, controller design of an MIMO plant with n inputs and n outputs could be, for example, decomposed into n independent single input-single output (SISO) subsystem designs. The effectiveness of the controller design procedure is initially verified through simulations of industrial examples.

A Gentle/S approach to robot assisted neuro-rehabilitation

Movement disorders (MD) include a group of neurological disorders that involve neuromotor systems. MD can result in several abnormalities ranging from an inability to move, to severe constant and excessive movements. Strokes are a leading cause of disability affecting largely the older people worldwide. Traditional treatments rely on the use of physiotherapy that is partially based on theories and also heavily reliant on the therapists training and past experience. The lack of evidence to prove that one treatment is more effective than any other makes the rehabilitation of stroke patients a difficult task. UL motor re-learning and recovery levels tend to improve with intensive physiotherapy delivery. The need for conclusive evidence supporting one method over the other and the need to stimulate the stroke patient clearly suggest that traditional methods lack high motivational content, as well as objective standardised analytical methods for evaluating a patient's performance and assessment of therapy effectiveness. Despite all the advances in machine mediated therapies, there is still a need to improve therapy tools. This chapter describes a new approach to robot assisted neuro-rehabilitation for upper limb rehabilitation. Gentle/S introduces a new approach on the integration of appropriate haptic technologies to high quality virtual environments, so as to deliver challenging and meaningful therapies to people with upper limb impairment in consequence of a stroke. The described approach can enhance traditional therapy tools, provide therapy "on demand" and can present accurate objective measurements of a patient's progression. Our recent studies suggest the use of tele-presence and VR-based systems can potentially motivate patients to exercise for longer periods of time. Two identical prototypes have undergone extended clinical trials in the UK and Ireland with a cohort of 30 stroke subjects. From the lessons learnt with the Gentle/S approach, it is clear also that high quality therapy devices of this nature have a role in future delivery of stroke rehabilitation, and machine mediated therapies should be available to patient and his/her clinical team from initial hospital admission, through to long term placement in the patient's home following hospital discharge.