La neurobiologie à l'origine d'un comportement social des consommateurs d'opiacés et des personnes dépendantes reste largement méconnue, entravant le développement de nouveaux traitements efficaces contre les troubles de l'utilisation des opiacés. Cependant, des preuves précliniques récentes suggèrent que le système du facteur de libération de la corticotrophine (CRF) pourrait être impliqué. Dans cette optique, nous avons utilisé la méthode des tâches à trois chambres (3-CH) ainsi qu'une méthode génétique et pharmacologique pour évaluer l’impact de l’administration de la morphine et du sevrage sur le comportement social des souris vis-à-vis de l'utilisation du système CRF. Dans une première série d'expériences, nous avons constaté que les sujets mâles manifestaient un intérêt pseudo-social accru suscité par l'hostilité pendant le sevrage des opiacés, ce qui indiquait les effets à long terme de l'administration chronique de médicaments sur le fonctionnement social normal. Par ailleurs, les femelles ont manifesté moins d’intérêt social lors du sevrage aux opiacés, un phénotype qui reproduit plus facilement ce qui a été observé chez l’homme. Notamment, le déficit en récepteurs CRF1 a complètement sauvé ce dernier déficit social, ajoutant ainsi aux preuves croissantes liant le système CRF aux dysfonctionnements comportementaux induits par la substance. Dans une deuxième série d'expériences, nous avons étudié plus largement les effets initiaux de la morphine sur les activités « naturellement » gratifiantes. Nous avons constaté qu'une seule et même administration aiguë d'une dose relativement faible du médicament suffisait à la fois à générer une récompense cérébrale et à induire de profonds déficits en intérêt social et en motivation liée à l'alimentation, fournissant ainsi des preuves expérimentales initiales du « détournement » du cerveau. Il est intéressant de noter que l'administration systémique d'antalarmine, antagoniste du récepteur de la CRF, a complètement inversé ce dernier déficit social, ce qui indique que le système CRF joue un rôle essentiel dans la médiation de la diminution de l'intérêt suscité par les substances pour des activités rémunératrices «naturellement» et renforce la notion de potentiel thérapeutique du ciblage de la CRF. / The neurobiology underlying poor social behavior of opiate users and dependent individuals remains largely unknown, hampering the development of noveleffective therapies for opiate use disorders. However, recent pre-clinical evidence suggests that the corticotropin-releasing factor (CRF) system might be involved.In this light, we employed the three-chamber (3-CH) task and genetic/pharmacological approaches to assess the impact of morphine administrationand withdrawal upon social behavior in mice with regard to the CRF system. In a first set of experiments, we found that male subjects displayed increasedhostility-driven pseudo-social interest during opiate withdrawal, indicative of longlasting effects of chronic drug administration upon normal social functioning. On theother hand, female subjects displayed lower social interest during opiate withdrawal, a phenotype that more straightforwardly replicates what observed in humans.Notably, CRF1 receptor-deficiency completely rescued the latter social deficit, adding to the growing evidence linking the CRF system to substance-induced behavioraldysfunctions. In a second set of experiments, we investigated the initial effects of morphine more widely on naturally” rewarding activities. We found that a single, acuteadministration of a relatively low dose of the drug was sufficient to produce brain reward and at the same time to induce profound deficits in social interest and fooddriven motivation, providing initial experimental evidence of “hijacking” of brain reward systems by substances of abuse. Interestingly, systemic administration of the CRF receptor antagonist antalarmin completely reversed the latter social deficit, indicating a critical role of the CRF system in mediating substance-induced decreased interest for “naturally” rewarding activities and strengthening the notion of a therapeutic potential for CRF-targeting pharmacological agents.

“Wer nicht wagt, der nicht gewinnt!” —hohe Gewinne sind oft unwahrscheinlich. Theorien der “Adaptiven Kognition” sagen voraus, dass ein solcher statistischer Zusammenhang aus der Welt kognitive Prozesse systematisch beeinflussen kann (u.A. Anderson, 1991; Brunswik, 1944; Gibson, 1979). Im 1. Kapitel gebe ich einen breit gefächerten Überblick warum dies der Fall sein kann. Im 2. Kapitel zeige ich experimentell, dass eine Korrelation zwischen Gewinnhöhe und Gewinnwahrscheinlichkeit Entscheidungen unter Unsicherheit (keine Gewinnwahrschenlichkeit gegeben) beeinflusst. Versuchspersonen schätzten die Gewinnwahrscheinlichkeit gemäß der Gewinnhöhe ein. Im 3. Kapitel zeige ich experimentell, dass Versuchspersonen durch die Korrelation zwischen Gewinnhöhe und Gewinnwahrscheinlichkeit Erwartungen aufbauten: War eine Option “überraschend”, z.B. da sie einen hohen Gewinn mit einer hohen Wahrscheinlichkeit verspricht, wurde eine solch überraschend gute Optionen länger evaluiert. Im 4. Kapitel beschäftige ich mich mit Entscheidungen unter Risiko. Mithilfe eines kognitiven Modells zeige ich, dass eine Struktur, in der hohe Gewinne sich als unwahrscheinlich erweisen, zu einer schnelleren, einfacheren Entscheidungsstrategie führen, als eine unkorrelierte Struktur. Im 5. Kapitel zeige ich, wie das von vielen Menschen angenommene “No free Lunch” Prinzip sich auf die Beurteilung von Risiken im Bereich klinischer Studien auswirkt: Hohe Vergütungen für klinische Studien können dazu führen, dass die Studie als riskanter und schlussendlich unethischer wahrgenommen wird. Zusammengefasst ergänzt die Arbeit ergänzt vorherige Forschung, indem sie zeigt, dass Gewinne und Wahrscheinlichkeiten nicht nur in der Welt systematisch miteinander verbunden sind, sondern auch in der menschlichen Kognition. Dies wirft ein neues Licht auf eine alte Frage: Wer entscheidet wann “rational”, und warum? / The large rewards that people desire are typically unlikely. Theories of adaptive cognition predict that such a regularity can systematically affect how the mind operates (e.g. Anderson, 1991; Brunswik, 1944; Gibson, 1979). In this dissertation, I theoretically and empirically examined how the link between risks and rewards affects judgments and decisions. In Chapter 1, I provide a broad theoretical overview. In Chapter 2, I show how people exploit risk–reward structures in decisions under uncertainty; that is, decisions in which probabilities are unavailable to the decision maker or difficult to ascertain. In these situations, people can infer the probabilities of events directly from the payoffs when risks and rewards are found to be correlated. Chapter 3 shows that risk–reward shapes how people evaluate options in decisions under risk. Surprising options that did not fit surrounding risk–reward structures were linked to longer response times and an increase in pupil size, particularly when options were “surprisingly good”—i.e., when they offered a high payoff and a high probability. Chapter 4 addresses how risk–reward structures affect decisions under risk in general. A computational model showed that risk–reward structures do not change (subjective) preferences in choices. Instead, risk–reward structures affect how people accumulate evidence in risky choice. Specifically, inversely related risks and rewards promote satisficing whereas uncorrelated risks and rewards promote maximizing. In Chapter 5, I provide an example of how risk–reward structures affect decision making in the wild. Specifically, I show that some individuals use very high pay as a cue to infer the potential risks a clinical trial poses. Taken together, this work suggests that people’s risk–reward priors should not be blindly assumed away, and challenges assumptions on who is considered rational and why.

Pour élucider les effets récompensants de la lumière, deux approches expérimentales ont été adoptées. Une étude chez le rongeur diurne Arvicanthis ansorgei indique que le raccourcissement de la longueur du jour avec la diminution de l'intensité lumineuse induit des changements du rythme de l’activité locomotrice, de la quantité de dopamine dans le système de la récompense et sur l'expression du gène Per2 dans le noyau suprachiasmatique. Ces altérations ont été améliorées par l'exposition journalière à des créneaux d’une heure de lumière à la fin du jour. Dans une étude humaine, le bien-être subjectif mesuré par d'échantillonnage de ressentis, a été corrélée avec des mesures de fluctuations lumineuses environnementales chez des participants en bonne santé et des insomniaques. Les résultats ont montré que le bien-être subjectif augmente proportionnellement à l'intensité de la lumière chez de jeunes en bonne santé contrairement à un déficit global en matière d'évaluation hédonique chez les insomniaques. De plus amples études devraient être menées afin d'élucider l'effet des signaux lumineux environnementaux sur les circuits de récompense. / To elucidate the reward effects of light, two experimental approaches have been adopted. An experiment for the study of the effects of exposure to a winter-like photoperiod on the diurnal rodent Arvicanthis ansorgei indicated that shortened day length with reduced light intensity induces a phase change in locomotor activity, alterations in the dopamine content in reward system structures, and alterations in the Per2 clock gene expression in the suprachiasmatic nucleus. These measures were improved by daily exposure to a one-hour pulse of light at late in the day. In a human model, subjective wellbeing, measured by experience sampling, was correlated with ambient luminosity measurements in participants with insomnia and healthy controls. Results indicated that subjective wellbeing increases with increasing light intensity in healthy young volunteers, in contrast to an overall deficit in reward evaluation in insomniacs. Light exposure should be taken into account as an important factor in determining the quality of life of insomniacs and in depression. Further studies should be conducted to elucidate the effect of ambient light signals on reward circuits.

Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2015-06-22T13:23:12Z No. of bitstreams: 1 LuizHenriqueFigueiraMarquezan.pdf: 938223 bytes, checksum: a0f654a722bdbab2d35f3dd82200a349 (MD5) / Made available in DSpace on 2015-06-22T13:23:12Z (GMT). No. of bitstreams: 1 LuizHenriqueFigueiraMarquezan.pdf: 938223 bytes, checksum: a0f654a722bdbab2d35f3dd82200a349 (MD5) Previous issue date: 2012 / Nenhuma / A separação entre propriedade e controle nas empresas origina a chamada relação de agenciamento, na qual os sócios (principal) delegam a autonomia das decisões a executivos contratados (agente). A Teoria de Agência, que estuda este fenômeno, tem como um de seus pressupostos o autointeresse das pessoas. Diante disso, um dos objetivos do controle de gestão é assegurar ou diminuir as eventuais divergências entre os interesses dos proprietários e dos executivos. Essa Teoria indica a concessão de incentivos, como a remuneração variável, com essa finalidade. Nesse contexto, este estudo propôs-se a estudar este fenômeno, sobre como funciona um sistema de remuneração variável para executivos utilizado como forma de controle de gestão. Para isso realizou-se uma pesquisa aplicada sobre a realidade de uma empresa, que atua no ramo de bebidas, e possui planos de remuneração variável por desempenho. Os procedimentos de coleta das evidências foram: observação direta; análise documental; e entrevistas semiestruturadas com dez executivos contemplados nestes planos. O tratamento dessas ocorreu por meio da combinação entre as técnicas de análise de conteúdo e de discurso. Dentre outros resultados, as evidências indicam que a empresa premia o desempenho com remuneração variável, por participações nos lucros e gratificações em dinheiro. Essas formas de recompensa, os momentos de pagamento ao final de cada ano, o uso de indicadores de desempenho financeiros, e o padrão de desempenho anual, combinados, podem gerar um problema de agência por direcionar o foco dos executivos ao curto prazo. Compensando isso, verificou-se o uso de uma forma de avaliar o processo do desenvolvimento profissional do executivo de forma qualitativa, com efeitos de curto e longo prazos. A composição de três planos de remuneração por desempenho propicia alinhamento de interesses: (a) entre executivos e os demais funcionários; (b) entre os executivos, por serem remunerados por metas que não apresentem divergências matemáticas e pelo uso de metas coletivas e organizacionais; (c) entre sócios e executivos tendo esses a maior possibilidade de remuneração variável vinculada ao alcance da meta principal para empresa, o indicador EBITDA. Quanto aos interesses, os executivos que são sócios demonstram tranquilidade quanto ao risco deste tipo de remuneração, apresentando preocupação maior com a continuidade da empresa a longo prazo. Constatou-se também que o desejo de possuir metas como desafios e o desenvolvimento profissional foram apontados como motivos dos executivos preferirem a remuneração variável. Além dos planos de remuneração, a presença de dois sócios entre os executivos indica redução da assimetria informacional e maior facilidade no processo de alinhamento dos interesses de ambos. / The separation of ownership and control in companies originating the call agency relationship, in which shareholders (principal) delegate decisions to empower executives hired (agent). The Agency Theory, which studies this phenomenon has as one of their self-interest of those assumptions. Thus, one of the goals of management control is to ensure or reduce any differences between the interests of owners and executives. Theory indicates that the granting of incentives such as variable pay, for this purpose. In this context, this study aimed to study this phenomenon, about how a variable compensation system for executives used as a form of management control. To this end we carried out a survey applied to the reality of a company, which operates in the beverage industry, and has variable remuneration plans for performance. The procedures for collection of evidence were: direct observation, document analysis and semistructured interviews with ten executives included in these plans. The treatment of these occurred through the combination of the techniques of content analysis and discourse. Among other results, the evidence indicates that the company rewards performance with variable pay for bonuses and cash bonuses. These forms of reward, the times of payment at the end of each year, the use of financial performance indicators, and the pattern of annual performance, combined, can create an agency problem by directing the focus of executives to the short term. Offsetting this, there was the use of a way to evaluate the process of professional development executive in a qualitative manner, with effects of short and long term. The composition of three plans pay for performance provides alignment of interests: (a) between executives and other employees, (b) between the executive, to be paid by targets that do not show differences by using mathematical and collective goals and organizational; (c) between these members and executives with the greatest possibility of variable compensation tied to the achievement of the ultimate goal for the company, the EBITDA. As for interests, executives who are members demonstrate tranquility about the risk of this type of compensation, showing more concern about the continuity of the company's long-term. It was also the desire to own goals and challenges and professional development were identified as reasons for preferring executive incentive compensation. In addition to the compensation plans, the presence of two members among executives indicates a reduction of information asymmetry and greater ease in aligning the interests of both.

Les récepteurs mu aux opioïdes (MORs) jouent un rôle central dans l’addiction et ce majoritairement via le contrôle qu’ils exercent sur les phénomènes de récompense. Les effets des MORs sur le système de récompense sont généralement attribués à leur expression dans le circuit mésocorticolimbique. Les MORs sont toutefois exprimés dans d’autres régions du cerveau, notamment dans une petite structure cérébrale épithalamique qui exprime la plus forte densité de MORs : l’habénula médiane (MHb). Le rôle de cette population spécifique de récepteurs n’a jamais été exploré, malgré l’implication fortement suggérée dans la littérature de l’habénula dans l’addiction et les processus de récompense/aversion sous-jacents. Nous avons donc généré un modèle de souris knockout conditionnel chez lesquelles nous supprimons les MORs uniquement dans l’habénula et nous les avons soumis à des tests comportementaux dans le but d’évaluer les fonctions de ces récepteurs et leur impact sur le comportement avec un focus sur les processus aversifs, cognitifs et récompensant. Nos résultats révèlent que les récepteurs mu que nous supprimons dans l’habénula limitent l’aversion somatique et affective mais ne modulent ni les réponses locomotrices, analgésiques et de récompense à la morphine, ni les fonctions cognitives que nous avons testées. Nous identifions donc pour la première fois une population de MORs dans l’habénula qui freinent l’aversion et nous suggérons par là-même que les récepteurs mu de l’habénula pourraient être cruciaux dans le stage «sevrage aversif» des cycles d’addiction. / Mu opioid receptors (MORs) have been extensively studied for their addictive properties that are thought to operate through the control of reward processes. While the importance of MORs in reward is generally attributed to their presence in the mesocorticolimbic circuitry, their role in the medial habenula (MHb), the structure in which MORs are most densely expressed, remains unexplored to date. This is quite surprising given the increasing literature on the habenula’s role in addiction as well as reward/aversion processes. Here we generated a conditional knockout mouse model that lacks MORs solely in the MH band we investigated the contribution of habenular MORs in brain functions and behavioural out comes with emphasis on reward, aversion and cognition. While the performance of our mutant model did not differ in locomotor, analgesic and reward responses to morphine norincognitive tasks compared to control mice, we uncovered a novel role for MORs in aversive states.This is the first report demonstrating that MORs control both somatic and affective aversion specifically at the level of the MHb. Habenular MORs could thus be crucial to the aversive with drawal stage of addiction cycles that is thought to increase craving and prevent success in quitting.

A goal of my dissertation is to find out current educational conditions of gifted children in Czech Republic. What legislative, financial and methodological proceedings of state policy influence education of talented children and their possible impact on schools. Another aim is to verify how important this educational field is attributed by headmasters at primary schools and what helps or complicates introducing methodical education of gifted pupils. The dissertation contains of three parts. The first one is theoretical which acquaints readers with educational field of talented children in the Czech Republic in sphere of legislative, including the glance abroad. Second part is an empirical questionnaire survey, based on interview detecting conditions for education of exceptionally gifted children at primary schools. It focuses on headmasters, their motivating, educating and evaluating of teachers and what advantages for school it brings. Another goal is to find out possibilities and differences in financing the work with talented children in particular regions. On the basis of established data is created a manual, which could help headmasters to introduce methodical education of gifted pupils. The manual is drawn up as a gradual successive approach.

Nyfikenhet är inneboende strävan mot inhämtande av ny information. Länge har det ansetts vedertaget att yttre motivation hämmar nyfikenhet, men på senare år har det framkommit forskning som indikerar ett delvis annorlunda förhållande. För att undersöka interaktionen mellan nyfikenhet och yttre motivation konstruerades ett bildbaserat inlärningsexperiment i vilket deltagarna belönades respektive bestraffades för att inhämta information som stillade deras nyfikenhet. I experimentets första del skattade deltagarna sin nyfikenhet på mosaikmaskerade bilder. I experimentets andra del presenterades de skattade mosaikbilderna med en konstant bild. De 24 deltagarnas uppgift var att välja en av de två bilderna i varje spelomgång. Bilden deltagarna valde demaskerades efter olika väntetider. Väntetiden var antingen dragen från en lång eller kort väntetidsfördelning och avhängig om bilden var ny eller återkommande. Huruvida det var den nya eller återkommande bilden som hade kort respektive lång medelväntetid varierade mellan de två inomgrupps-betingelserna. Deltagarna antogs vara yttre motiverade att minimera väntetiden genom att lära sig och sedan föredra den bildkategori med kortast genomsnittlig väntetid. Deltagarna antogs dessutom vara nyfikna att se bilder demaskerade. I ena betingelsen sammanföll deltagarnas yttre motivation och nyfikenhet, i andra betingelsen var deltagarnas yttre motivation och nyfikenhet i konflikt. I en tredje kontrollbetingelse var nyfikenhetsdimensionen eliminerad för att mäta inlärning av väntetid. Experimentet visade att det krävdes fler spelomgångar för att lära sig väntetiden i kontrollbetingelsen jämfört med betingelsen där nya bilder också hade kortare medelväntetid. Betingelsen där nya bilder var förknippade med längre medelväntetid delade deltagarna i två grupper. Deltagare i den ena gruppen valde sällan nya bilder (proportionsmått: 0.75 – 1.0) medan deltagare i den andra gruppen valde nya bilder i hög utsträckning (proportionsmått: 0.0077 – 0.069). Dessa grupper utmärks också på personlighetsdrag kopplade till nyfikenhet. Sammantaget ger studien stöd för att nyfikenhet och yttre motivation kan integreras och att personlighetsdrag är relaterade till värderingen av information. / Curiosity is an intrinsic aspiration to obtain new information. It has been considered that external motivation inhibits curiosity, but over the last years new research has indicated a partially different relationship. To investigate the interaction between curiosity and external motivation a picture-based learning experiment was constructed, in which the participants were rewarded, alternatively punished for obtaining new information which pleased their curiosity. In the first part of the experiment, the participants scored their curiosity of mosaic-covered pictures. In the second part of the of the experiment, the scored mosaic-covered pictures were consequently presented next to a constant picture. The task for the 24 participants was then to choose one of the pictures in each round. The chosen mosaic-covered picture would then show according to a certain waiting time - either short or long - depending on if it was new or recurring. Whether the new or recurring picture had a short or long average waiting time varied between the two in-group conditions. It was hypothesized that the participants would be externally motivated to minimize the waiting time by learning and favouring the category of pictures with the shortest waiting time. In addition, it was hypothesized that the participants would be curious of the mosaic-covered pictures. In one of the conditions, the participants external motivation coincided with their curiosity, in the other condition the external motivation was in conflict with their curiosity. In a third controlling condition, the dimension of curiosity was eliminated to measure the learning of the waiting time. The experiment showed that more rounds are needed to learn the waiting time in the controlling conditions compared to when the new pictures also had a shorter average waiting time. When new pictures were associated with a longer average waiting time, it divided the participants into two groups. In one group the participant rarely chose new pictures (proportion: 0.75 – 1.0) while the participants in the other group to a large extent chose new pictures (proportion: 0.0077 – 0.069). These differences were also shown in the participants personal traits connected to curiosity. All together, the study supports the idea that curiosity and external motivation can be integrated and that personal traits are related to the evaluation of information.

A hipóxia-isquemia (HI) encefálica neonatal pode gerar sequelas neurológicas permanentes nos indivíduos que sobrevivem a este evento precoce. Dentre estas sequelas, o diagnóstico de Transtorno de déficit de atenção e hiperatividade (TDAH) já foi relacionado em pesquisa clínica. Sabendo que não há consenso de um modelo adequado para o estudo do TDAH em pesquisa experimental, novas abordagens que contribuam para o desenvolvimento desse modelo são necessárias. Assim, o objetivo do presente estudo foi investigar se a HI neonatal contribui para o desenvolvimento das características comportamentais relacionadas ao TDAH na fase adulta em ratos e correlacionar os resultados comportamentais com o volume da lesão encefálica. Para isso, ratos Wistar machos foram divididos em dois grupos: hipóxia-isquemia (HI, n=12) e controle (CT, n=10). O procedimento de HI consistiu na combinação da oclusão da artéria carótida comum direita no 7º dia pós-natal com exposição a uma atmosfera hipóxica (8% O2 e 92% N2, durante 90 minutos). Durante a fase adulta, ao atingir dois meses de idade, os animais foram testados no teste attentional set-shifting (ASS) para avaliar flexibilidade comportamental atencional e no teste de tolerância ao atraso da recompensa, para avaliação da escolha impulsiva. Os resultados mostraram que os animais submetidos à HI apresentaram prejuízo na função executiva, avaliado no ASS, evidenciado por uma inflexibilidade comportamental quando a regra para a execução da tarefa era mudada (p ≤ ,05 para o número de tentativas para passar dos estágios de Reversão 2 e Reversão 3, assim como o número de erros nesses estágios, além do estágio de mudança extradimensional – Teste t não-pareado). No teste de tolerância ao atraso da recompensa, não foi observada uma maior impulsividade dos animais HI, tendo os dois grupos um comportamento similar neste teste. Além disso, as avaliações do volume encefálico pelo Método de Cavalieri demonstraram uma atrofia no grupo HI no hemisfério total, córtex cerebral, substância branca, hipocampo e estriado, principalmente no lado ipsilateral à lesão (p ≤ ,05, Teste t não-pareado). Considerando esses resultados, podemos inferir que a HI neonatal é um fator ambiental que pode contribuir para o desenvolvimento das características comportamentais observadas no TDAH, e que estas são associadas a uma atrofia encefálica geral. / Neonatal hypoxic-ischemic encephalopathy (HI) can cause permanent neurological sequelae in survivors of this early event. Among these sequelae, the diagnosis of attention deficit hyperactivity disorder (ADHD) has already been linked in clinical research. There is no consensus about an ideal ADHD model in experimental research, being necessary new approaches that contribute to the development of this model. Thus, the aim of this study was to investigate whether HI contributes to the development of characteristics related to ADHD in adult rats and correlate the behavioral results with brain damage volume. Male Wistar rats were divided into two groups: hypoxia-ischemia (HI, n=12) and control (CT, n=10). The HI procedure consist of a permanent occlusion of the right common carotid artery followed by a period of hypoxia (90 min; 8% O2 and 92% N2), at seventh postnatal day (PND). Two months later, animals were evaluated in attentional set-shifting test (ASS) for assessment of attentional flexibility and in the tolerance to delay of reward, for evaluation of impulsivity choice. Our results demonstrated that animals submitted to HI manifest impairments in executive function, evidenced by a behavioral inflexibility when the rule for the execution of the ASS task was changed (p ≤ ,05 for number of trials to reach the criterion in Reversion 2 and 3 stages, as well as in number of erros in these stages, in addition to the Extradimensional shift stage – Unpaired t test). In the tolerance to delay of reward, no greater impulsivity of HI animals was observed, with both groups demonstrating similar behavior in this task. Moreover, the assessments of brain volume by Cavalieri method demonstrated atrophy in HI group in total hemisphere, cerebral cortex, white matter, hippocampus and striatum, especially on the side ipsilateral to the lesion (p ≤ ,05 – Unpaired t test). Considering these results, we can infer that neonatal HI is an environmental factor that could contribute to the development of behavioral characteristics observed in ADHD which are associated to general brain atrophy.

In the last decade, (non)prescription opioid abuse, opioid use disorder (OUD) diagnoses, and opioid-related overdoses have risen and represent a significant public health concern. One method of understanding OUD is as a disorder of choice that requires choosing opioid rewards at the expense of other nondrug rewards. The characterization of OUD as a disorder of choice is important as it implicates decision- making processes as therapeutic targets, such as the valuation of opioid rewards. However, reward-value measurement and interpretation are traditionally different in substance abuse research compared to related fields such as economics, animal behavior, and neuroeconomics and may be less effective for understanding how opioid rewards are valued. The present research therefore used choice procedures in line with behavioral/neuroeconomic studies to determine if drug-associated decision making could be predicted from economic choice theories. In Experiment 1, rats completed an isomorphic food-food probabilistic choice task with dynamic, unpredictable changes in reward probability that required constant updating of reward values. After initial training, the reward magnitude of one choice subsequently increased from one to two to three pellets. Additionally, rats were split between the Signaled and Unsignaled groups to understand how cues modulate reward value. After each choice, the Unsignaled group received distinct choice-dependent cues that were uninformative of the choice outcome. The Signaled group also received uninformative cues on one option, but the alternative choice produced reward-predictive cues that informed the trial outcome as a win or loss. Choice data were analyzed at a molar level using matching equations and molecular level using reinforcement learning (RL) models to determine how probability, reward magnitude, and reward-associated cues affected choice. Experiment 2 used an allomorphic drug versus food procedure where the food reward for one option was replaced by a self-administered remifentanil (REMI) infusion at doses of 1, 3 and 10 μg/kg. Finally, Experiment 3 assessed the potential for both REMI and food reward value to be commonly scaled within the brain by examining changes in nucleus accumbens (NAc) Oxygen (O2) dynamics. Results showed that increasing reward probability, magnitude, and the presence of reward-associated cues all independently increased the propensity of choosing the associated choice alternative, including REMI drug choices. Additionally, both molar matching and molecular RL models successfully parameterized rats’ decision dynamics. O2 dynamics were generally commensurate with the idea of a common value signal for REMI and food with changes in O2 signaling scaling with the reward magnitude of REMI rewards. Finally, RL model-derived reward prediction errors significantly correlated with peak O2 activity for reward delivery, suggesting a possible neurological mechanism of value updating. Results are discussed in terms of their implications for current conceptualizations of substance use disorders including a potential need to change the discourse surrounding how substance use disorders are modeled experimentally. Overall, the present research provides evidence that a choice model of substance use disorders may be a viable alternative to the disease model and could facilitate future treatment options centered around economic principles.

Cette thèse de doctorat propose une analyse empirique des microfondations des phénomènes monétaires macroéconomiques, et plus particulièrement des processus d'apprentissage et capacités cognitives requis pour qu'un équilibre émerge dans une économie expérimentale implémentantun modèle de prospection monétaire. Dans ce but, nous avons "opérationalisé" le modèle original de Kiyotaki et Wright et modélisé le comportement de sujets humains à l'aide de différents algorithmes d'apprentissage par renforcement. Nous montrons que les données comportementales sont mieux expliquées par les modèles d'apprentissage par renforcement que par les prédictions des équilibres théoriques, et que la spéculation monétaire semble s'appuyer sur la considération de coûts d'opportunité. Nos résultats constituent une nouvelle étape dans la compréhension des processus d'apprentissage à l'oeuvre dans la prise de décision multiple en économie et des microfondations cognitives de l'utilisation macroéconomique de la monnaie. Parallèlement, cette thèse de doctorat comprend une analyse plus précise de l'une des composantes fondamentales de l'apprentissage par renforcement à savoir, le processus de mise à jour des valeurs. A travers deux études, nous montrons graduellement que ce processus est biaisé en faveur des informations confirmatoires. En effet, nous avons trouvé que des sujets réalisant diverses tâches d'apprentissage probabiliste prenaient en compte préférentiellement les informations qui confirmaient leur pensée initiale. Ces résultats permettent une meilleure compréhension des biais d'optimisme et de confirmation au niveau neuro-computationnel. / This dissertation proposes to analyze empirically the microfoundations of the macroeconomic use of money, more particularly the human learning processes and cognitive abilities requiredfor a monetary equilibrium to emerge in an experimental economy implementing a search theoretical paradigm of money emergence. To achieve this, we operationalized the original Kiyotaki and Wright search model and fitted real subjects' behaviors with different reinforcement learning algorithms. We show that reinforcement learning better explains behavioral datain comparison to theoretical equilibria predictions, and highlight the importance of opportunity costs to implement a speculative use of money. Our results constitute a new step towards the understanding of learning processes at work in multi-step economic decision making and ofthe cognitive microfoundations of the macro-economic use of money. In parallel, this dissertation also compounds in-depth analyses of one of the core components of reinforcement learning,namely the update process. In two studies, we gradually show that the latter is biased positively towards confirmatory information. Indeed, we found that subjects performing different probability learning tasks preferentially took into account information that confirme dtheir initial thoughts in contrast to information that contradicted them. These results constitute a step towards the understanding of the genesis of optimism and confirmation biases at the neurocomputational level.