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Des interventions ciblant l’amélioration cognitive sont de plus en plus à l’intérêt dans nombreux domaines, y compris la neuropsychologie. Bien qu'il existe de nombreuses méthodes pour maximiser le potentiel cognitif de quelqu’un, ils sont rarement appuyé par la recherche scientifique. D’abord, ce mémoire examine brièvement l'état des interventions d'amélioration cognitives. Il décrit premièrement les faiblesses observées dans ces pratiques et par conséquent il établit un modèle standard contre lequel on pourrait et devrait évaluer les diverses techniques ciblant l'amélioration cognitive. Une étude de recherche est ensuite présenté qui considère un nouvel outil de l'amélioration cognitive, une tâche d’entrainement perceptivo-cognitive : 3-dimensional multiple object tracking (3D-MOT). Il examine les preuves actuelles pour le 3D-MOT auprès du modèle standard proposé. Les résultats de ce projet démontrent de l’augmentation dans les capacités d’attention, de mémoire de travail visuel et de vitesse de traitement d’information. Cette étude représente la première étape dans la démarche vers l’établissement du 3D-MOT comme un outil d’amélioration cognitive. / Cognitive enhancement is a domain of burgeoning interest in many domains including neuropsychology. While there are different methods that exist in order to achieve cognitive enhancement, there are few that are supported by research. The current work examines the state of cognitive enhancement interventions. It first outlines the weaknesses observed in these practices and then proposes a standard template for assessing cognitive enhancement tools. A research study is then presented that examines a novel cognitive enhancement tool, 3-dimensional multiple object tracking (3D-MOT), and weighs the current evidence for 3D-MOT against the proposed standard template. The results of the current work demonstrate that 3D-MOT is effective in enhancing attention, working memory and visual information processing speed, and represent a first step toward establishing 3D-MOT as a cognitive enhancement tool.

O aprimoramento cognitivo farmacológico refere-se ao uso de medicamentos por pessoas saudáveis para melhorar o funcionamento do cérebro e aprimorar o desempenho cognitivo. Um dos medicamentos mais utilizados no Brasil com esta finalidade é o cloridrato de metilfenidato, comercializado com o nome de Ritalina ou Concerta. Ele tem sido utilizado por universitários, empresários e profissionais da saúde que visam aumentar a capacidade produtiva para cumprir prazos e metas. Considerando que esta prática está se disseminando na sociedade e chegando aos alunos do ensino médio, optou-se por fazer um estudo cujo objetivo foi caracterizar a percepção de alunos do 3º ano do ensino médio de escolas públicas, privadas e profissionalizantes e de cursinhos públicos e privados das cidades de Juazeiro do Norte (CE), Fortaleza (CE) e São Paulo (SP), sobre o uso de medicamentos para aprimoramento cognitivo, buscando identificar condições preditoras ao uso dessas substâncias. Para atingir tal objetivo o procedimento de coleta de dados foi composto de duas etapas: a primeira desenvolveu-se por meio de um estudo quali-quantitativo, com aplicação de questionários, que buscou evidenciar um panorama geral sobre o tema, sendo realizada com 534 sujeitos oriundos do 3º ano do ensino médio de escolas públicas, privadas e profissionalizantes e de cursinhos públicos e privados das cidades de Juazeiro do Norte (CE), Fortaleza (CE) e São Paulo (SP). A partir dos dados colhidos foi realizada uma segunda etapa com 13 alunos da escola profissionalizante da cidade de Juazeiro do Norte (CE), com abordagem qualitativa e realização de grupo focal, que buscou aprofundar o entendimento dessas questões. No tratamento de dados da primeira etapa utilizou-se o teste não paramétrico Qui-quadrado, e na segunda etapa a Análise de Conteúdo. Os resultados apontaram que os alunos querem ingressar no ensino superior, mais do que outras opções, consideram esta a principal função da escola e se consideram preparados para tal. Trabalhar não é seu desejo imediato e por isso não consideram importante que a escola os prepare para tanto. A compreensão de fundamentos científico-tecnológicos e o aprimoramento como pessoa humana foram considerados aspectos importantes. Medicamentos para aprimoramento foram vistos como algo positivo que poderia ser usado às vésperas do vestibular; para ajudar nos momentos de pressão por parte dos pais e da escola, em que se sentem sobrecarregados pelas suas obrigações; para conseguir realizar múltiplas atividades; para garantir energia e concentração. Verificou-se ainda que dispor de informações sobre medicamentos e conhecer usuários predispõe a um possível uso. A possibilidade de consumir os medicamentos está presente em todas as cidades analisadas e em todas as instituições. Quando tiveram a oportunidade de pensar melhor sobre o tema e falar sobre ele nos grupos focais, os alunos conseguiram perceber os fatores envolvidos na adesão ao uso de substâncias, e o que leva os estudantes a consumi-las. Os dados levantados evidenciaram que os participantes se mostraram curiosos em relação a uma substância ainda desconhecida para muitos, mas que em suas fantasias pode ser interessante para ajudar a atingir seus objetivos. Conclui-se que este é um tema relevante e preocupante; por isso, sua discussão em diferentes meios deve ser aprofundada / Pharmacological cognitive enhancement refers to the use of drugs by healthy individuals aiming at brain functioning improvement and cognitive performance enhancement. One of the widely used drugs in Brazil with these aims is methylphenidate hydrochloride, marketed under the name of Ritalina or Concerta. It has been used by college students, businessmen and health professionals aiming at enhancing their productive capacity to meet deadlines and goals. Considering the dissemination of this practice reaching high school students, this study was held aiming at characterizing the perception of high-school final-year students from public, private and vocational schools and public and private pre-college preparatory courses in the cities of Juazeiro do Norte (CE), Fortaleza (CE) and São Paulo (SP) on the use of drugs for cognitive enhancement, searching to identify predictive conditions to the use of such substances. For such, the procedure for data collection comprised two stages: the first was developed through a quali-quantitative study, searching to demonstrate a general panorama on the theme, with questionnaires applied to 534 individuals in the final year of high school in public, private and vocational schools and public and private pre-college preparatory courses in the cities of Juazeiro do Norte (CE), Fortaleza (CE) and São Paulo (SP). A second stage was held using the collected data for a qualitative approach and focus group with thirteen students from the vocational school in Juazeiro do Norte (CE), searching to deeply comprehend such issues. For data processing, non-parametric chi-square test was used in the first stage, and Content Analysis in the second one. Results indicated that the students wish to apply for university education, more than other options, consider this the main function of the school, and consider themselves prepared for this goal. Working is not their immediate wish and, for this reason, they do not deem important that the schools provide them with training for it. Comprehension of scientific-technological fundamentals and their enhancement as human beings were considered as important aspects. Enhancement drugs were deemed something positive that could be used on the eve of entrance examinations; to help in moments of pressure from parents and school when they feel overwhelmed by their duties; to be able to perform multiple activities; to ensure energy and focus. It was verified that they are predisposed to a possible use when provided with information and acquainted to other users. The possibility to consume such medicines is present in all analyzed cities and institutions. When faced with the opportunity to think more on the theme and talk about it in focus groups, students could perceive the factors involved in the adhesion to the use of substances and what drives them to its consumption. Collected data revealed that the participants were curious about a substance yet unknown to many of them, but imagined that it might be interesting to use it to reach their goals. It is concluded that the theme is relevant and worrisome; for this reason, the discussion about it in different backgrounds must be deepened

O aprimoramento cognitivo farmacológico refere-se ao uso de medicamentos por pessoas saudáveis para melhorar o funcionamento do cérebro e aprimorar o desempenho cognitivo. Um dos medicamentos mais utilizados no Brasil com esta finalidade é o cloridrato de metilfenidato, comercializado com o nome de Ritalina ou Concerta. Ele tem sido utilizado por universitários, empresários e profissionais da saúde que visam aumentar a capacidade produtiva para cumprir prazos e metas. Considerando que esta prática está se disseminando na sociedade e chegando aos alunos do ensino médio, optou-se por fazer um estudo cujo objetivo foi caracterizar a percepção de alunos do 3º ano do ensino médio de escolas públicas, privadas e profissionalizantes e de cursinhos públicos e privados das cidades de Juazeiro do Norte (CE), Fortaleza (CE) e São Paulo (SP), sobre o uso de medicamentos para aprimoramento cognitivo, buscando identificar condições preditoras ao uso dessas substâncias. Para atingir tal objetivo o procedimento de coleta de dados foi composto de duas etapas: a primeira desenvolveu-se por meio de um estudo quali-quantitativo, com aplicação de questionários, que buscou evidenciar um panorama geral sobre o tema, sendo realizada com 534 sujeitos oriundos do 3º ano do ensino médio de escolas públicas, privadas e profissionalizantes e de cursinhos públicos e privados das cidades de Juazeiro do Norte (CE), Fortaleza (CE) e São Paulo (SP). A partir dos dados colhidos foi realizada uma segunda etapa com 13 alunos da escola profissionalizante da cidade de Juazeiro do Norte (CE), com abordagem qualitativa e realização de grupo focal, que buscou aprofundar o entendimento dessas questões. No tratamento de dados da primeira etapa utilizou-se o teste não paramétrico Qui-quadrado, e na segunda etapa a Análise de Conteúdo. Os resultados apontaram que os alunos querem ingressar no ensino superior, mais do que outras opções, consideram esta a principal função da escola e se consideram preparados para tal. Trabalhar não é seu desejo imediato e por isso não consideram importante que a escola os prepare para tanto. A compreensão de fundamentos científico-tecnológicos e o aprimoramento como pessoa humana foram considerados aspectos importantes. Medicamentos para aprimoramento foram vistos como algo positivo que poderia ser usado às vésperas do vestibular; para ajudar nos momentos de pressão por parte dos pais e da escola, em que se sentem sobrecarregados pelas suas obrigações; para conseguir realizar múltiplas atividades; para garantir energia e concentração. Verificou-se ainda que dispor de informações sobre medicamentos e conhecer usuários predispõe a um possível uso. A possibilidade de consumir os medicamentos está presente em todas as cidades analisadas e em todas as instituições. Quando tiveram a oportunidade de pensar melhor sobre o tema e falar sobre ele nos grupos focais, os alunos conseguiram perceber os fatores envolvidos na adesão ao uso de substâncias, e o que leva os estudantes a consumi-las. Os dados levantados evidenciaram que os participantes se mostraram curiosos em relação a uma substância ainda desconhecida para muitos, mas que em suas fantasias pode ser interessante para ajudar a atingir seus objetivos. Conclui-se que este é um tema relevante e preocupante; por isso, sua discussão em diferentes meios deve ser aprofundada / Pharmacological cognitive enhancement refers to the use of drugs by healthy individuals aiming at brain functioning improvement and cognitive performance enhancement. One of the widely used drugs in Brazil with these aims is methylphenidate hydrochloride, marketed under the name of Ritalina or Concerta. It has been used by college students, businessmen and health professionals aiming at enhancing their productive capacity to meet deadlines and goals. Considering the dissemination of this practice reaching high school students, this study was held aiming at characterizing the perception of high-school final-year students from public, private and vocational schools and public and private pre-college preparatory courses in the cities of Juazeiro do Norte (CE), Fortaleza (CE) and São Paulo (SP) on the use of drugs for cognitive enhancement, searching to identify predictive conditions to the use of such substances. For such, the procedure for data collection comprised two stages: the first was developed through a quali-quantitative study, searching to demonstrate a general panorama on the theme, with questionnaires applied to 534 individuals in the final year of high school in public, private and vocational schools and public and private pre-college preparatory courses in the cities of Juazeiro do Norte (CE), Fortaleza (CE) and São Paulo (SP). A second stage was held using the collected data for a qualitative approach and focus group with thirteen students from the vocational school in Juazeiro do Norte (CE), searching to deeply comprehend such issues. For data processing, non-parametric chi-square test was used in the first stage, and Content Analysis in the second one. Results indicated that the students wish to apply for university education, more than other options, consider this the main function of the school, and consider themselves prepared for this goal. Working is not their immediate wish and, for this reason, they do not deem important that the schools provide them with training for it. Comprehension of scientific-technological fundamentals and their enhancement as human beings were considered as important aspects. Enhancement drugs were deemed something positive that could be used on the eve of entrance examinations; to help in moments of pressure from parents and school when they feel overwhelmed by their duties; to be able to perform multiple activities; to ensure energy and focus. It was verified that they are predisposed to a possible use when provided with information and acquainted to other users. The possibility to consume such medicines is present in all analyzed cities and institutions. When faced with the opportunity to think more on the theme and talk about it in focus groups, students could perceive the factors involved in the adhesion to the use of substances and what drives them to its consumption. Collected data revealed that the participants were curious about a substance yet unknown to many of them, but imagined that it might be interesting to use it to reach their goals. It is concluded that the theme is relevant and worrisome; for this reason, the discussion about it in different backgrounds must be deepened

Le vaste domaine de l’amélioration cognitive traverse les applications comportementales, biochimiques et physiques. Aussi nombreuses sont les techniques que les limites de ces premières : des études de pauvre méthodologie, des pratiques éthiquement ambiguës, de faibles effets positifs, des effets secondaires significatifs, des couts financiers importants, un investissement de temps significatif, une accessibilité inégale, et encore un manque de transfert. L’objectif de cette thèse est de proposer une méthode novatrice d’intégration de l’une de ces techniques, le neurofeedback, directement dans un paradigme d’apprentissage afin d’améliorer la performance cognitive et l’apprentissage. Cette thèse propose les modalités, les fondements empiriques et des données à l’appui de ce paradigme efficace d’apprentissage ‘bouclé’. En manipulant la difficulté dans une tâche en fonction de l’activité cérébrale en temps réel, il est démontré que dans un paradigme d’apprentissage traditionnel (3-dimentional multiple object tracking), la vitesse et le degré d’apprentissage peuvent être améliorés de manière significative lorsque comparés au paradigme traditionnel ou encore à un groupe de contrôle actif. La performance améliorée demeure observée même avec un retrait du signal de rétroaction, ce qui suggère que les effets de l’entrainement amélioré sont consolidés et ne dépendent pas d’une rétroaction continue. Ensuite, cette thèse révèle comment de tels effets se produisent, en examinant les corrélés neuronaux des états de préparation et de performance à travers les conditions d’état de base et pendant la tâche, de plus qu’en fonction du résultat (réussite/échec) et de la difficulté (basse/moyenne/haute vitesse). La préparation, la performance et la charge cognitive sont mesurées via des liens robustement établis dans un contexte d’activité cérébrale fonctionnelle mesurée par l’électroencéphalographie quantitative. Il est démontré que l’ajout d’une assistance- à-la-tâche apportée par la fréquence alpha dominante est non seulement appropriée aux conditions de ce paradigme, mais influence la charge cognitive afin de favoriser un maintien du sujet dans sa zone de développement proximale, ce qui facilite l’apprentissage et améliore la performance. Ce type de paradigme d’apprentissage peut contribuer à surmonter, au minimum, un des limites fondamentales du neurofeedback et des autres techniques d’amélioration cognitive : le manque de transfert, en utilisant une méthode pouvant être intégrée directement dans le contexte dans lequel l’amélioration de la performance est souhaitée. / The domain of cognitive enhancement is vast, spanning behavioral, biochemical and physical applications. The techniques are as numerous as are the limitations: poorly conducted studies, ethically ambiguous practices, limited positive effects, significant side-effects, high financial costs, significant time investment, unequal accessibility, and lack of transfer. The purpose of this thesis is to propose a novel way of integrating one of these techniques, neurofeedback, directly into a learning context in order to enhance cognitive performance and learning. This thesis provides the framework, empirical foundations, and supporting evidence for a highly efficient ‘closed-loop’ learning paradigm. By manipulating task difficulty based on a measure of cognitive load within a classic learning scenario (3-dimentional multiple object tracking) using real-time brain activity, results demonstrate that over 10 sessions, speed and degree of learning can be substantially improved compared with a classic learning system or an active sham-control group. Superior performance persists even once the feedback signal is removed, which suggests that the effects of enhanced training are consolidated and do not rely on continued feedback. Next, this thesis examines how these effects occur, exploring the neural correlates of the states of preparedness and performance across baseline and task conditions, further examining correlates related to trial results (correct/incorrect) and task difficulty (slow/medium/fast speeds). Cognitive preparedness, performance and load are measured using well-established relationships between real-time quantified brain activity as measured by quantitative electroencephalography. It is shown that the addition of neurofeedback-based task assistance based on peak alpha frequency is appropriate to task conditions and manages to influence cognitive load, keeping the subject in the zone of proximal development more often, facilitating learning and improving performance. This type of learning paradigm could contribute to overcoming at least one of the fundamental limitations of neurofeedback and other cognitive enhancement techniques : a lack of observable transfer effects, by utilizing a method that can be directly integrated into the context in which improved performance is sought.

Mémoire en recherche-création / L’usage de smart drugs pour améliorer les capacités cognitives est devenu un problème majeur depuis les années 1970 et revêt une importance croissante dans le contexte moderne (Denis, 2021). Ce mémoire explore les motifs d’usage de psychotropes à des fins de performance parmi les programmeurs. L’objectif principal est de comprendre si l’usage des substances vise principalement l’amélioration personnelle et le dépassement de soi, ou si elle découle de problématiques plus complexes et multifactorielles. Pour y parvenir, la méthodologie repose sur une approche qualitative en trois étapes : 1) Netnographie — analyse de 40 fils de discussion sur un forum de programmeurs pour appréhender de manière globale la profession et les motivations liées à cette utilisation; 2) Entretiens semi-structurés — réalisation de quatre entretiens avec des programmeurs pour comprendre leurs expériences professionnelles, les compétences requises, les pressions subies et les défis rencontrés. Les entretiens ont été transcrits, codés dans le logiciel Nvivo et soumis à une analyse thématique; 3) Triangulation des données – croisement et confrontation des informations des deux premières étapes afin d’approfondir l’analyse du phénomène, améliorer la compréhension, et renforcer la validité et la fiabilité des résultats. Les données analysées révèlent que les programmeurs font face à des pressions professionnelles accrues, avec des motivations de consommation allant de la recherche de performance à la gestion du stress. Toutefois, une pression sociétale valorisant la réussite personnelle et professionnelle sous-tend ce contexte. / The use of smart drugs to enhance cognitive abilities has become a major issue since the 1970s and is of increasing importance in the modern context (Denis, 2021). This dissertation explores the motives for performance-enhancing psychotropic drug use among programmers. The main objective is to understand whether substance use is primarily aimed at self-improvement and self-transcendence, or whether it stems from more complex, multifactorial issues. To achieve this, the methodology is based on a three-stage qualitative approach: 1) Netnography - analysis of 40 discussion threads on a programmers' forum to gain an overall understanding of the profession and the motivations associated with this use; 2) Semi-structured interviews - conducting four interviews with programmers to understand their professional experiences, the skills required, the pressures experienced and the challenges encountered. The interviews were transcribed, coded in Nvivo software and subjected to thematic analysis; 3) Data triangulation – cross-referencing and confrontation of information from the first two stages in order to deepen analysis of the phenomenon, improve understanding, and reinforce the validity and reliability of results. The data analyzed reveals that programmers are facing increased professional pressures, with consumer motivations ranging from the quest for performance to stress management. However, a societal pressure to value personal and professional success underpins this context.

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. / Sensory cortex is an essential area where sensory perception occurs. Especially visual cortex processes visual information transmitted from the retina through the thalamus. By different neuronal activation the information is segregated and sent to diverse visual area for interpretation. Neurons are the basic unit that transform sensory information into electrophysiological signal, transfer to the cortex and integrate it. Connection between neurons can be modulated depending on the persistent presynaptic activity inducing either a long-term increase or decrease of the post-synaptic activity. Modification in synaptic strength can affect large area and induce reorganization of cortical map (i.e. cortical plasticity) which changes the representation of the visual stimulus and its weight in visual processing. Cortical plasticity can occur during juvenile while forming developmental connection or in adult while acquiring novel information (i.e. learning). The neurotransmitter ACh is involved in many cognitive functions, such as learning or attention and it was demonstrated that lesioning or blocking cholinergic system diminishes cortical plasticity. It was shown that nicotinic, M1 subtype and M2 subtype muscarinic receptors are the major cholinergic receptors abundant in the cortex and implicated during cortical plasticity induction. In a first part, I analyzed visual evoked potentials (VEPs) in V1 of rats during a 4-8h period after coupling visual stimulation to an intracortical injection of ACh agonist carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually injected muscarinic, nicotinic, α7, and NMDA receptor antagonists just before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude for long-term. Pre-inhibition of muscarinic, nicotinic and NMDA receptor completely abolished this long-term enhancement, while α7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness which involves nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex. These mechanisms were similar to long-term potentiation, a neurobiological mechanism of learning. In a second step, I evaluate whether cholinergic modulation of visual neurons results in cortical activity and visual perception changes. Awake adult rats were exposed repetitively for two weeks to an orientation-specific grating with coupling visual stimulation to an electrical stimulation of the basal forebrain. The visual acuity, as measured using a visual water maze before and after coupling visual/cholinergic stimulation was increased. The increase in visual acuity was not observed when visual or basal forebrain stimulation was performed separately nor when cholinergic fibers were selectively lesioned prior to the visual stimulation. There was a long-lasting increase in cortical reactivity of the primary visual cortex shown by c-Fos immunoreactivity of both pyramidal and GABAergic interneuron. These findings demonstrate that when coupled with visual training, the cholinergic system improves visual performance for the trained orientation probably through enhancement of attentional processes and cortical plasticity in V1 related to the ratio of excitatory/inhibitory inputs. Finally, I also investigated the different pharmacological mechanisms involved in the visual enhancement. Pre- and post-pairing visual/cholinergic stimulation VEP were compared with selective administered agonist/antagonist during the pairing. Awaken adult rats were exposed during 10 minutes per day for 1 week to an orientation specific grating with an electrical stimulation of the basal forebrain. Intracortical injection of different pharmacological agents during pairing demonstrated that nicotinic and M1 muscarinic receptors are used to amplify cortical response while M2 muscarinic receptor suppresses GABAergic neurons to disinhibit excitatory neurons. Infusion of GABAergic antagonist supported that inhibitory system is crucial to induce cortical plasticity. These findings demonstrate that visual training coupled with the cholinergic stimulation enhances the cortical plasticity mediated by nicotinic, M1 and M2 muscarinic receptors, which the latter induces a disinhibition by suppressing GABAergic neuron. The cholinergic system is a potent neuromodulatory system. Boosting this system during perceptual learning robustly enhances the sensory perception. Especially, pairing a cholinergic activation with a visual stimulation increases the signal-to-noise ratio, cue detection ability in the primary visual cortex. This cholinergic enhancement increases the strength of thalamocortical afferent to facilitate the treatment of a novel stimulus while decreasing the cortico-cortical signaling to minimize recurrent or top-down modulation. This is mediated by different cholinergic receptor subtypes located in both glutamatergic and GABAergic neurons of the different cortical layers. The mechanisms of cholinergic enhancement are closely linked to attentional processes, long-term potentiation and modulation of the excitatory/inhibitory balance. The present thesis shows that electrical stimulation of the basal forebrain has similar effect with cholinergic agonist release and pairing visual/cholinergic stimulation induces cortical plasticity. Repetitive pairing of visual/cholinergic increases visual discrimination capacity and enhances perceptual ability. This enhancement is followed by an augmentation of neuronal activity demonstrated by c-Fos immunohistochemistry. Immunoreactivity also shows difference in glutamatergic and GABAergic neurons activities between layers. Pharmacological injection during visual/cholinergic pairing suggests that nicotinic and M1 muscarinic receptor can amplify excitatory response while M2 receptor controls GABAergic activation. Altogether cholinergic system activated during visual process induces cortical plasticity and can enhance perceptual ability. Further understanding of this training has the potential to accelerate visual recovery or boost cognitive function.

L’émergence de l’utilisation du méthylphénidate (MPH; Ritalin) par des étudiants universitaires afin d’améliorer leur concentration et leurs performances universitaires suscite l’intérêt du public et soulève d’importants débats éthiques auprès des spécialistes. Les différentes perspectives sur l’amélioration des performances cognitives représentent une dimension importante des défis sociaux et éthiques autour d’un tel phénomène et méritent d’être élucidées. Ce mémoire vise à examiner les discours présents dans les reportages internationaux de presse populaire, les discours en bioéthique et en en santé publique sur le thème de l’utilisation non médicale du méthylphénidate. Cette recherche a permis d’identifier et d’analyser des « lacunes » dans les perspectives éthiques, sociales et scientifiques de l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive d’individus en santé. Une analyse systématique du contenu des discours sur l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive a identifié des paradigmes divergents employés pour décrire l’utilisation non médicale du méthylphénidate et discuter ses conséquences éthiques. Les paradigmes « choix de mode de vie », « abus de médicament » et « amélioration de la cognition » sont présents dans les discours de la presse populaire, de la bioéthique et de la santé publique respectivement. Parmi les principales différences entre ces paradigmes, on retrouve : la description de l’utilisation non médicale d’agents neuropharmacologiques pour l’amélioration des performances, les risques et bénéfices qui y sont associés, la discussion d’enjeux éthiques et sociaux et des stratégies de prévention et les défis associés à l’augmentation de la prévalence de ce phénomène. La divergence de ces paradigmes reflète le pluralisme des perceptions de l’utilisation non médicale d’agents neuropharmacologiques Nos résultats suggèrent la nécessité de débats autour de l’amélioration neuropharmacologique afin de poursuivre l’identification des enjeux et de développer des approches de santé publique cohérentes. / The non-medical use of neuropharmaceuticals has sparked ethical debates. For example, there is mounting evidence that methylphenidate (MPH; Ritalin) is being used by healthy university students to improve concentration, alertness, and academic performance, a phenomenon known as cognitive enhancement. The different perspectives on the ethics of cognitive enhancement represent an important dimension of the social and ethical challenges related to such practices but have yet to be examined thoroughly. This thesis aimed to assess existing positive and negative reports in international print media, bioethics literature, and public health literature on the use of MPH to identify and analyze gaps in the ethical, social, and scientific perspectives about the non-medical use of MPH for cognitive enhancement in healthy individuals. A systematic content analysis of discourses on the non-medical use of methylphenidate for cognitive enhancement identified divergent frameworks employed to describe the non-medical use of methylphenidate and discuss its ethical implications: The frameworks of “lifestyle choice”, “prescription drug abuse” and “cognitive enhancement” are present in print media, bioethics, and public health discourses respectively. Important differences between frameworks include the description of the non-medical use of neuropharmaceuticals for cognitive enhancement, associated risks and benefits, discussion of ethical and social issues surrounding the phenomenon and the prevention strategies and challenges to the widespread use of neuropharmaceuticals for cognitive enhancement. Diverging frameworks reflect pluralism in perceptions if the non-medical use of neuropharmaceuticals for cognitive enhancement. At this time, unacknowledged pluralism and implicit assumptions about cognitive enhancement may impede public health interventions and ethics discussions.

L’émergence de l’utilisation du méthylphénidate (MPH; Ritalin) par des étudiants universitaires afin d’améliorer leur concentration et leurs performances universitaires suscite l’intérêt du public et soulève d’importants débats éthiques auprès des spécialistes. Les différentes perspectives sur l’amélioration des performances cognitives représentent une dimension importante des défis sociaux et éthiques autour d’un tel phénomène et méritent d’être élucidées. Ce mémoire vise à examiner les discours présents dans les reportages internationaux de presse populaire, les discours en bioéthique et en en santé publique sur le thème de l’utilisation non médicale du méthylphénidate. Cette recherche a permis d’identifier et d’analyser des « lacunes » dans les perspectives éthiques, sociales et scientifiques de l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive d’individus en santé. Une analyse systématique du contenu des discours sur l’utilisation non médicale du méthylphénidate pour accroître la performance cognitive a identifié des paradigmes divergents employés pour décrire l’utilisation non médicale du méthylphénidate et discuter ses conséquences éthiques. Les paradigmes « choix de mode de vie », « abus de médicament » et « amélioration de la cognition » sont présents dans les discours de la presse populaire, de la bioéthique et de la santé publique respectivement. Parmi les principales différences entre ces paradigmes, on retrouve : la description de l’utilisation non médicale d’agents neuropharmacologiques pour l’amélioration des performances, les risques et bénéfices qui y sont associés, la discussion d’enjeux éthiques et sociaux et des stratégies de prévention et les défis associés à l’augmentation de la prévalence de ce phénomène. La divergence de ces paradigmes reflète le pluralisme des perceptions de l’utilisation non médicale d’agents neuropharmacologiques Nos résultats suggèrent la nécessité de débats autour de l’amélioration neuropharmacologique afin de poursuivre l’identification des enjeux et de développer des approches de santé publique cohérentes. / The non-medical use of neuropharmaceuticals has sparked ethical debates. For example, there is mounting evidence that methylphenidate (MPH; Ritalin) is being used by healthy university students to improve concentration, alertness, and academic performance, a phenomenon known as cognitive enhancement. The different perspectives on the ethics of cognitive enhancement represent an important dimension of the social and ethical challenges related to such practices but have yet to be examined thoroughly. This thesis aimed to assess existing positive and negative reports in international print media, bioethics literature, and public health literature on the use of MPH to identify and analyze gaps in the ethical, social, and scientific perspectives about the non-medical use of MPH for cognitive enhancement in healthy individuals. A systematic content analysis of discourses on the non-medical use of methylphenidate for cognitive enhancement identified divergent frameworks employed to describe the non-medical use of methylphenidate and discuss its ethical implications: The frameworks of “lifestyle choice”, “prescription drug abuse” and “cognitive enhancement” are present in print media, bioethics, and public health discourses respectively. Important differences between frameworks include the description of the non-medical use of neuropharmaceuticals for cognitive enhancement, associated risks and benefits, discussion of ethical and social issues surrounding the phenomenon and the prevention strategies and challenges to the widespread use of neuropharmaceuticals for cognitive enhancement. Diverging frameworks reflect pluralism in perceptions if the non-medical use of neuropharmaceuticals for cognitive enhancement. At this time, unacknowledged pluralism and implicit assumptions about cognitive enhancement may impede public health interventions and ethics discussions.