The ability to take effective decisions is fundamental for successful environmental adaptation and survival. In this thesis, I investigated situations in which decisions appear irrational, at least from certain standpoints. I conducted a behavioural decision-making experiment in two groups of macaques: controls and a group with ventromedial prefrontal cortex/medial orbitofrontal cortex (vmPFC/ mOFC) lesions. Some choices lead to compound outcomes composed of different constituent parts. Control macaques' decisions suggested their estimates of the value of the compound were biased away from the sum of the values of the constituents and towards their mean. Lesions of vmPFC/mOFC diminished the size of the effect so that macaques in some ways appeared to make more rational decisions. Based on the results of this experiment I devised a similar Functional Magnetic Resonance Imaging (fMRI) paradigm with the control animals. This demonstrated strong vmPFC/mOFC activity when similar decisions were made and suggested a value comparison process. In addition, I investigated the role of dopamine in learning using Fast-Scan Cyclic Voltammetry (FSCV), while rats performed a simple decision-making task. Theories about the role of dopamine in learning have focused on the possibility that it codes scalar reward value prediction errors. Less consideration has been given to the possibility that dopamine might reflect prediction errors about reward identities regardless of value. I measured dopamine in the nucleus accumbens when unexpected changes in reward value or identity occurred while rats executed a two-choice two-reward instrumental task. Dopamine levels in the nucleus accumbens reflected reward value prediction errors. In addition, however, they also reflected some information about reward identity under some circumstances. Further investigation suggested that this might be due to differences in the nutritional value of different reward types that did not have clear measurable impacts of behaviour in the tasks that I used.

Executive functioning is a multidimensional concept encompassing higher-order adaptive abilities, such as judgment, decision-making, self-monitoring, planning, and emotional regulation. Disruption in executive functioning often results in devastating impairments in vitally-important areas of life, such as one's ability to hold employment and maintain social relationships. Executive functions have been associated primarily with the prefrontal cortex. However, the nature and degree of the association between frontal lobe damage and performance on executive functioning tests remains controversial. Research suggests that the association may vary based on the specific location of damage within the prefrontal cortex, as well as the used measure of executive functioning. Few investigations have systematically addressed these variables. The current study employed the lesion method to investigate the relationship between performance on a battery of executive functioning tests and damage to specific regions of the prefrontal cortex. Three groups of participants with lesions in one of the locations of interest [ventromedial prefrontal (VMPC, n = 14), dorsolateral prefrontal (DLPC, n = 14), and non-frontal (n = 18)] were administered the Delis-Kaplan Executive Function System (D-KEFS, 2001), a comprehensive battery of executive functioning tests. Results revealed no statistically-significant differences between group performances on the D-KEFS primary measures. However, a qualitative analysis of the results revealed several meaningful group differences. It appears that some relationship exists between frontal lobe damage, particularly in the DLPC, and decreased performance on several executive functioning tests but further research overcoming the methodological limitations of most existing literature on this topic is needed to clearly resolve this issue.

As teorias mais influentes acerca do funcionamento do córtex pré-frontal (PFC) tomam essa estrutura como um córtex de associação e de integração de informações oriundas de outras estruturas nervosas. Isso implicaria na participação direta do PFC nos processos de memória operacional e em processo atencionais. Estudos hodológicos e neurofisiológicos sugerem, que o córtex orbitofrontal (OFC) seria responsável pela integração de informações de caráter sensorial, motivacional e afetivo, enquanto o córtex pré-frontal ventromedial (vmPFC) seria diretamente ligado ao OFC, tendo um papel crucial na codificação de estímulos emocionais oriundos da amígdala. Nesse contexto, é aceito que a integração das informações feita por essas estruturas seja essencial para o processo de tomada de decisões, uma vez que esse comportamento necessita de uma avaliação do ambiente em termos de comparações de situações novas a experiências prévias armazenadas na memória, assim como um balanço entre custos, benefícios e cálculo de possíveis valores da recompensa. Para testar essas hipóteses, ratos com danos seletivos no vmPFC foram submetidos testes de avaliação de ansiedade e medo condicionado no paradigma de teste e reteste no labirinto em cruz elevado (LCE), assim como a testes de memória de referência espacial e memória operacional no labirinto aquático de Morris. Outro grupo de animais teve matrizes de multi-eletrodos implantadas no OFC para a avaliação da atividade neuronal dessa estrutura em um teste envolvendo tomada de decisões, no qual devem escolher entre ganhar 1 pellet de chocolate imediatamente ou 4 pellets envolvendo atrasos variados. No teste no LCE, animais com lesão no vmPFC diferem dos animais controle por apresentarem uma diminuição do tempo de avaliação de risco sem apresentar alterações nos parâmetros que aferem memória, atividade locomotora e ansiedade. No teste de memória de referência espacial após treinamento extensivo de busca pela plataforma em um mesmo local no labirinto aquático, animais com lesão persistem no local quando se retira a plataforma (probe test). Já no teste de memória operacional, no qual a localização da plataforma é alterada diariamente, esses animais não diferem do grupo controle. Na tarefa envolvendo tomada de decisões, observou-se uma atividade eletrofisiológica de neurônios do OFC relacionada ao momento crítico no qual o animal deve realizar uma escolha. Em conjunto, esses resultados mostram que o vmPFC está relacionado à flexibilidade comportamental e tomada de decisões, possivelmente em conjunto com o OFC, cuja atividade neuronal sugere uma participação nos processos de tomada de decisões e de elaboração de estratégias / The most influential theories on the function of the prefrontal cortex (PFC) suggest that this structure is an association cortex, responsible for integration of information received from other parts of the brain. This would implicate in direct participation of the PFC in working memory and attentional processes. Given this context, hodological and neurophysiological studies suggest that the orbitofrontal cortex (OFC) would be responsible for the integration of sensory, motivational and affective aspects, while the ventromedial prefrontal cortex (vmPFC), which is directly connected to the OFC, would have a key role in encoding emotional stimuli from the amygdala. It is well accepted that the processing of these aspects of information is crucial for decision-making processes, given the fact that this expression of behavior requires an evaluation of the environment in terms of comparing novel situation to previous experiences, as well as processing the balance between costs, outcomes and reward values. In order to test these hypotheses, rats with selective lesions to the vmPFC were subjected to the elevated plus maze (EPM) to evaluate anxiety and conditioned fear in the test retest paradigm. Animal were also tested in a spatial reference memory and a working memory tasks in the Morris water maze. Another group of rats had multi-electrode arrays chronically implanted in the OFC for the evaluation of the neuronal activity during a decision-making task, in which the animals had to choose between a small reward of one chocolate pellet immediately and a large reward of four chocolate pellets after varying delays. The results of the EPM show that animals with lesion to the vmPFC differ from control animals by showing diminished time evaluating risk in the second exposure to the EPM, without damage to locomotor activity, memory and anxiety levels. In the reference spatial memory task in the water maze, after extensive training searching for the hidden platform in the same location, lesioned animals persisted searching for the platform in that particular location after it was removed (probe test). However, in the working memory task, in which the platform is presented in a different location each day, lesioned animals did not differ from control animals. In the decision-making task, differential electrophysiological activity in OFC neurons was observed, particularly in the moment of the task in which the animal was required to perform the choice between rewards. Together, these results suggest that the vmPFC is related to behavioral flexibility and decision-making, possibly acting together with the OFC, which neuronal activity suggests participation in decision-making processes

As teorias mais influentes acerca do funcionamento do córtex pré-frontal (PFC) tomam essa estrutura como um córtex de associação e de integração de informações oriundas de outras estruturas nervosas. Isso implicaria na participação direta do PFC nos processos de memória operacional e em processo atencionais. Estudos hodológicos e neurofisiológicos sugerem, que o córtex orbitofrontal (OFC) seria responsável pela integração de informações de caráter sensorial, motivacional e afetivo, enquanto o córtex pré-frontal ventromedial (vmPFC) seria diretamente ligado ao OFC, tendo um papel crucial na codificação de estímulos emocionais oriundos da amígdala. Nesse contexto, é aceito que a integração das informações feita por essas estruturas seja essencial para o processo de tomada de decisões, uma vez que esse comportamento necessita de uma avaliação do ambiente em termos de comparações de situações novas a experiências prévias armazenadas na memória, assim como um balanço entre custos, benefícios e cálculo de possíveis valores da recompensa. Para testar essas hipóteses, ratos com danos seletivos no vmPFC foram submetidos testes de avaliação de ansiedade e medo condicionado no paradigma de teste e reteste no labirinto em cruz elevado (LCE), assim como a testes de memória de referência espacial e memória operacional no labirinto aquático de Morris. Outro grupo de animais teve matrizes de multi-eletrodos implantadas no OFC para a avaliação da atividade neuronal dessa estrutura em um teste envolvendo tomada de decisões, no qual devem escolher entre ganhar 1 pellet de chocolate imediatamente ou 4 pellets envolvendo atrasos variados. No teste no LCE, animais com lesão no vmPFC diferem dos animais controle por apresentarem uma diminuição do tempo de avaliação de risco sem apresentar alterações nos parâmetros que aferem memória, atividade locomotora e ansiedade. No teste de memória de referência espacial após treinamento extensivo de busca pela plataforma em um mesmo local no labirinto aquático, animais com lesão persistem no local quando se retira a plataforma (probe test). Já no teste de memória operacional, no qual a localização da plataforma é alterada diariamente, esses animais não diferem do grupo controle. Na tarefa envolvendo tomada de decisões, observou-se uma atividade eletrofisiológica de neurônios do OFC relacionada ao momento crítico no qual o animal deve realizar uma escolha. Em conjunto, esses resultados mostram que o vmPFC está relacionado à flexibilidade comportamental e tomada de decisões, possivelmente em conjunto com o OFC, cuja atividade neuronal sugere uma participação nos processos de tomada de decisões e de elaboração de estratégias / The most influential theories on the function of the prefrontal cortex (PFC) suggest that this structure is an association cortex, responsible for integration of information received from other parts of the brain. This would implicate in direct participation of the PFC in working memory and attentional processes. Given this context, hodological and neurophysiological studies suggest that the orbitofrontal cortex (OFC) would be responsible for the integration of sensory, motivational and affective aspects, while the ventromedial prefrontal cortex (vmPFC), which is directly connected to the OFC, would have a key role in encoding emotional stimuli from the amygdala. It is well accepted that the processing of these aspects of information is crucial for decision-making processes, given the fact that this expression of behavior requires an evaluation of the environment in terms of comparing novel situation to previous experiences, as well as processing the balance between costs, outcomes and reward values. In order to test these hypotheses, rats with selective lesions to the vmPFC were subjected to the elevated plus maze (EPM) to evaluate anxiety and conditioned fear in the test retest paradigm. Animal were also tested in a spatial reference memory and a working memory tasks in the Morris water maze. Another group of rats had multi-electrode arrays chronically implanted in the OFC for the evaluation of the neuronal activity during a decision-making task, in which the animals had to choose between a small reward of one chocolate pellet immediately and a large reward of four chocolate pellets after varying delays. The results of the EPM show that animals with lesion to the vmPFC differ from control animals by showing diminished time evaluating risk in the second exposure to the EPM, without damage to locomotor activity, memory and anxiety levels. In the reference spatial memory task in the water maze, after extensive training searching for the hidden platform in the same location, lesioned animals persisted searching for the platform in that particular location after it was removed (probe test). However, in the working memory task, in which the platform is presented in a different location each day, lesioned animals did not differ from control animals. In the decision-making task, differential electrophysiological activity in OFC neurons was observed, particularly in the moment of the task in which the animal was required to perform the choice between rewards. Together, these results suggest that the vmPFC is related to behavioral flexibility and decision-making, possibly acting together with the OFC, which neuronal activity suggests participation in decision-making processes

Les mécanismes cérébraux engagés dans la prise de décision sont loin d’être compris. Ils peuvent cependant être décomposés en plusieurs étapes : il s’agit premièrement d’assigner une « valeur » aux options considérées, c’est-à-dire une quantification subjective du désir d’obtenir chacune d’entre elles. Ensuite, il faut les comparer afin d’être capable de sélectionner celle qui a la plus grande valeur. L’assignation d’une valeur à un objet semble être effectuée par un réseau cérébral qui recoupe le réseau de la récompense identifié chez l’animal et il a été logiquement nommé le « système cérébral des valeurs ». Le travail réalisé dans cette thèse s’intéresse à la notion de valeur et aux moyens d’y avoir accès, aux propriétés du réseau cérébral d’évaluation et à son implication dans le processus de décision. La première étude a montré que les moyens utilisés pour mesurer les valeurs pouvaient être considérés comme équivalents. La deuxième étude, réalisée sur des données d’intra-électroencéphalographie humaine, a permis d’étudier la dynamique neurale du réseau cérébral d’évaluation, mais aussi d’étudier ses propriétés. La dernière expérience, faite en IRMf propose une solution générale sur l’implémentation neurale du processus de décision et révèle des mécanismes sources de biais dans le comportement jusqu’ici inexplorés. Les résultats de ces études considérés dans leur ensemble mettent en lumière certains mécanismes cognitifs de la prise de décision en explorant les propriétés neurales d’assignation de valeurs mais également en proposant un nouveau cadre d’implémentation de la décision elle-même. / Neural processes engaged in decision-making remain unclear. A decomposition of these processes might help us to understand the involved mechanisms. Indeed, first we need to assign what we will call a ‘subjective value’ to each option – i.e. the quantification of how much we like each of these options. Then, we need to compare those values to finally being able to select one of them. Assigning a value seems to be the function of an interesting brain network which overlaps the reward circuitry identified in animal studies – and which is called the Brain Valuation System (BVS). In the first study of this PhD thesis, we investigated and compared three behavioral ways to have an access to these ‘subjective values’. We found that subjective values were relatively robust to the way they were elicited. In the second study, we investigated the specific properties of the Brain Valuation System established through fMRI in humans in a large dataset of intra-EEG recordings in epileptic patients. Finally, in the last study we investigated how this brain network was involved during a binary choice in fMRI. Altogether, our findings shed light on the distinct cognitive mechanisms underlying value-based decision-making i) by exploring the neural properties of value assignment and ii) by proposing a general solution to the neural implementation of the comparison between option values. We believe this demonstration points to hidden default policies as sources of bias in choices.

Deficient self-control leads to shortsighted decisions and incurs severe personal and societal costs. Although neuroimaging has advanced our understanding of neural mechanisms underlying self-control, the ecological validity of laboratory tasks used to assess self-control remains largely unknown. To increase ecological validity and to test a specific hypothesis about the mechanisms underlying real-life self-control, we combined functional MRI during valuebased decision-making with smartphone-based assessment of real-life self-control in a large community sample (N = 194). Results showed that an increased propensity to make shortsighted decisions and commit self-control failures, both in the laboratory task as well as during real-life conflicts, was associated with a reduced modulation of neural value signals in the ventromedial prefrontal cortex in response to anticipated long-term consequences. These results constitute the first evidence that neural mechanisms mediating anticipations of future consequences not only account for self-control in laboratory tasks but also predict real-life self-control, thereby bridging the gap between laboratory research and real-life behavior.

No description available.

Choisir entre l'action ou l'inaction est peut-être le type de décision le plus critique auquel un animal peut faire face. Une formalisation simple de ces choix consiste à évaluer les bénéfices attendus (nourriture, argent par exemple) ainsi que les coûts (punitions, pertes de temps ou d'argent) associés à chaque action et d'optimiser le rapport entre récompenses reçues et coûts assumés. Notre motivation à s'engager dans une action donnée dépend donc de la valeur de ce rapport. Dans le domaine de l'économie comportementale, l’optimisation de ce rapport bénéfices/coûts constitue le principe fondamental qui régule et explique le comportement des individus. Dans mes travaux de thèse, j'ai réalisé une implémentation de ces concepts venant de l'économie comportementale en utilisant une forme expérimentalement quantifiable de coûts: l'effort physique. Dans notre vie de tous les jours, si l'on nous demande de choisir entre deux options rapportant les même bénéfices mais demandant différents efforts (par exemple, travailler 3 ou 7 jours par semaine pour le même salaire), nous choisissons habituellement l'option qui nécessite la plus petite dépense d'énergie, en optant donc pour le moindre effort. Néanmoins, l'effort physique a été beaucoup moins étudié en comparaison à d'autres formes de coûts comme le fait de différer la récompense ou d'en augmenter l'incertitude. Le présent travail de recherche a donc pour but de mettre en lumière les bases neurales de la balance récompense / effort dans la prise de décision. Comprendre comment l'effort affecte la dévaluation des potentielles récompenses a un intérêt particulier pour la prise de décisions économiques mais aussi pour la clinique, étant donné que la diminution de la capacité à accepter d'avoir à exercer un effort est un symptôme-clé de nombreuses pathologies comme l'apathie ou la dépression. Nous faisons l’hypothèse que de tels désordres pourraient résulter de deux différents processus comportementaux: (a) une diminution de la sensibilité aux bénéfices futurs et/ou (b) une sensibilité excessive aux coûts potentiels. Ainsi, lorsqu'interrogés sur les raisons pour lesquelles ils ne veulent pas aller au cinéma regarder un film qu'ils apprécient, les patients apathiques peuvent déclarer que (a) le film n'est pas assez bon (soit une plus faible réponse à la valeur attendue), (b) le cinéma est trop loin (soit une plus forte sensibilité à l'effort anticipé). Afin de tester ces hypothèses, nous avons enregistré l'activité de neurones chez le singe pendant des tâches comportementales. Nous avons trouvé que d'une part, la dopamine encode la valeur de l'action future et oriente le comportement vers l'option demandant le moindre effort. D'autre part, la noradrénaline permet à l'individu de faire face à l'effort à venir en réduisant la sensibilité à l'anticipation de l'effort. En utilisant une approche pharmacologique, nous avons démontré que lorsque le niveau de noradrénaline est augmenté, les singes exercent d'avantage d'effort. En outre, nous avons montré que les potentiels locaux de champ dans le cortex pré-frontal ventro-médian, enregistrés dans une tâche comportementale identique, sont modulés par la valeur attendue et prédisent le choix du singe. En résumé, ce travail permet de départager en partie les circuits neuronaux impliqués dans le calcul de la balance récompense / effort, principalement encodée par les neurones dopaminergiques et dans les potentiels locaux de champ au niveau du cortex pré-frontal ventro-médian. Enfin, ce travail souligne le rôle de la noradrénaline dans la mobilisation de l'énergie d'un individu afin de faire face au défi que représente l'effort physique. / There is perhaps no more critical factor for the behaviour of an animal than the way it chooses between action and inaction. A simple way to formalise such choices is to evaluate the predicted benefit (e.g. food, money) and costs (e.g. punishments, losses, delays) associated with each action and optimise the rates at which rewards are received and costs avoided. Our motivation to perform a given action depends upon such value ratio. In the current behavioural economics literature, the optimisation of the benefits/costs ratio stands as the fundamental principle that regulates and explains agents’ behaviour. In my Ph.D. studies, I implement a realistic model of such concepts from behavioural economics by using an empirical type of cost: physical effort. In our everyday life, if we are asked to choose between two options that imply the same reward but different efforts (e.g., working 3 or 7 days per week for the same salary), we usually opt for the alternative that requires the slightest energy expenditure, thus the least effort. However, physical effort has been far less studied compared to other decision costs such as delay or uncertainty. The present Ph.D. work aims at highlighting the neuronal bases of such reward/effort tradeoff. Understanding how effort cost affects the discounting of potential rewards has a clear significance for economic decisions and clinics, since the reduced willingness to exert effort is a key signature of several clinical disorders such as apathy and depression We suggest that disorders such as apathy could result from two different behavioural processes: (a) a decreased responsiveness to future benefits and/or (b) an excessive sensitivity to potential costs. For instance, when asked why they would not go see a movie they like, patients may say that (a) the movie is not good enough (i.e. low responsiveness to expected value) or that (b) the theatre is too far away (i.e. high sensitivity to anticipated effort). To test our hypothesis, we combined behavioural tasks and pharmacological approach with neuron recordings in monkeys, targeting specifically two majors actors of the rewarding and effort system, dopamine and noradrenaline. We found that dopamine and noradrenaline have distinct but complementary roles. On the one hand, dopamine tracks the reward value of future outcomes and orient the behaviour towards the least effortful options. On the other hand, noradrenaline enables subjects to face the effort at hand, reducing the sensitivity to anticipated effort. Using a pharmacological approach, we found that, when we increase noradrenaline, monkeys exerted significantly more effort. Moreover, we have found that local field potentials in the ventromedial prefrontal cortex recorded in the same task encode the expected value and predict action selection. In summary, this Ph.D. work allows to disentangle some of the neuronal circuits implicated in the computation of the reward/effort tradeoff, mainly encoded by dopaminergic neurons and in the local field potential of the ventromedial prefrontal cortex. On the other hand, this work highlights the role of noradrenaline in the energization of behaviour to face the challenge represented by the physical effort.

Theory of Mind (ToM) is the ability to infer others’ mental states and thus to predict their behavior (Perner, 1991). Therefore, ToM is essential for the adequate adjustment of behavior in social situations. ToM can be divided into: 1) cognitive ToM encompassing inferences about intentions and beliefs and 2) affective ToM encompassing inferences about emotions (Shamay-Tsoory, Harari, Aharon-Peretz, & Levkovitz, 2010). Well-functioning skills of both ToM aspects are much-needed in the developmental period of adolescence because in this age phase peer relationships become more important and romantic relationships arise (Steinberg & Morris, 2001). Importantly, affective psychopathological disorders often have their onset in adolescence. ToM development in adolescence might be based on underlying cognitive mechanisms such as the ability to inhibit one’s own thoughts in order to understand another person’s thoughts (Carlson & Moses, 2001). Another possible mechanism relates to functional brain development across adolescence (Blakemore, 2008). Therefore, neurocognitive mechanisms may underlie ongoing ToM development in adolescence. First studies indicate an ongoing behavioral and functional brain development of ToM (e.g. Blakemore, 2008). However, ToM development in adolescence and how this might relate to underlying (neuro)cognitive functions remains largely underexamined. The major aims of the current thesis were first to answer the overall question whether there is an ongoing development of ToM in adolescence. This question relates to both behavioral and functional brain development. As a second major aim, the present work sought to elucidate possible (neuro)cognitive mechanisms of ongoing ToM development across adolescence. Specifically, these cognitive mechanisms might be basic cognitive functions as well as executive functions. Additionally, the present work aimed at exploring potential (neuro)cognitive mechanisms through an integration of both behavioral and functional brain studies. The current experimental work spans three cross-sectional studies investigating adolescents (aged around 12-15 years) and young adults (aged around 18-22 years) to examine for the first time both the behavioral (studies I and II) and functional brain development of ToM (study III) in adolescence and its underlying (neuro)cognitive mechanisms. In all three studies, more complex, advanced ToM tasks were employed to avoid ceiling effects. Study I was aimed at investigating if cognitive and affective ToM continues to develop in adolescence and at exploring if basic cognitive variables such as verbal ability, speed of processing, and working memory capacity underlie such development. Hence, two groups of adolescents and young adults completed tasks of ToM and basic cognitive abilities. Large age effects were revealed on both measures of ToM: adolescents performed lower than adults. These age differences remained significant after controlling for basic cognitive variables. However, verbal ability covaried with performance in affective ToM. Overall, results support the hypothesis of an ongoing development of ToM from adolescence to adulthood on both cognitive and affective aspects. Results may further indicate verbal ability being a basic cognitive mechanism of affective ToM. Study II was designed to further explore if affective ToM, as measured with a dynamic realistic task, continues to develop across adolescence. Importantly, this study sought to explore executive functions as higher cognitive mechanisms of developing affective ToM across adolescence. A large group spanning adolescents and young adults evaluated affective mental states depicted by actors in video clips. Additionally, participants were examined with three subcomponents of executive functions, inhibition, updating, and shifting following the classification of Miyake et al. (2000). Affective ToM performance was positively related to age and all three executive functions. Specifically, inhibition explained the largest amount of variance in age related differences of affective ToM performance. Overall, these results indicate the importance of inhibition as key underlying mechanism of developing an advanced affective ToM in adolescence. Study III set out to explore the functional brain development of affective ToM in adolescence by using functional magnetic resonance imaging (fMRI). The affective ToM measure was the behavioral developmentally sensitive task from study II. An additional control condition consisted of the same emotional stimuli with the instruction to focus on physical information. This study faced methodical challenges of developmental fMRI studies by matching performance of groups. The ventromedial prefrontal cortex (vMPFC) was significantly less deactivated in adolescents in comparison to adults, which might suggest that adolescents seem to rely more on self-referential processes for affective ToM. Furthermore, adolescents compared to adults showed greater activation in the dorsolateral prefrontal cortex (DLPFC) in the control condition, indicating that adolescents might be distracted by the emotional content and therefore needed to focus more on the physical content of the stimulus. These findings suggest affective ToM continues to develop on the functional brain level and reveals different underlying neurocognitive strategies for adolescents in contrast to adults. In summary, the current thesis investigated whether ToM continues to develop in adolescence until young adulthood and explored underlying (neuro)cognitive mechanisms. Findings suggest that there is indeed an ongoing development of both the cognitive and affective aspect of ToM, which importantly contributes to the conceptual debate. Moreover, the second benefit to the debate is to demonstrate how this change may occur. As a basic cognitive mechanism verbal ability and as an executive functioning mechanism inhibition was revealed. Furthermore, neurocognitive mechanisms in form of different underlying neurocognitive strategies of adolescents compared to adults were shown. Taken together, ToM development in adolescence seems to mirror a different adaptive cognitive style in adolescence (Crone & Dahl, 2012). This seems to be important for solving the wealth of socio-emotional developmental tasks that are relevant for this age span.

Theory of Mind (ToM) is the ability to infer others’ mental states and thus to predict their behavior (Perner, 1991). Therefore, ToM is essential for the adequate adjustment of behavior in social situations. ToM can be divided into: 1) cognitive ToM encompassing inferences about intentions and beliefs and 2) affective ToM encompassing inferences about emotions (Shamay-Tsoory, Harari, Aharon-Peretz, & Levkovitz, 2010). Well-functioning skills of both ToM aspects are much-needed in the developmental period of adolescence because in this age phase peer relationships become more important and romantic relationships arise (Steinberg & Morris, 2001). Importantly, affective psychopathological disorders often have their onset in adolescence. ToM development in adolescence might be based on underlying cognitive mechanisms such as the ability to inhibit one’s own thoughts in order to understand another person’s thoughts (Carlson & Moses, 2001). Another possible mechanism relates to functional brain development across adolescence (Blakemore, 2008). Therefore, neurocognitive mechanisms may underlie ongoing ToM development in adolescence. First studies indicate an ongoing behavioral and functional brain development of ToM (e.g. Blakemore, 2008). However, ToM development in adolescence and how this might relate to underlying (neuro)cognitive functions remains largely underexamined. The major aims of the current thesis were first to answer the overall question whether there is an ongoing development of ToM in adolescence. This question relates to both behavioral and functional brain development. As a second major aim, the present work sought to elucidate possible (neuro)cognitive mechanisms of ongoing ToM development across adolescence. Specifically, these cognitive mechanisms might be basic cognitive functions as well as executive functions. Additionally, the present work aimed at exploring potential (neuro)cognitive mechanisms through an integration of both behavioral and functional brain studies. The current experimental work spans three cross-sectional studies investigating adolescents (aged around 12-15 years) and young adults (aged around 18-22 years) to examine for the first time both the behavioral (studies I and II) and functional brain development of ToM (study III) in adolescence and its underlying (neuro)cognitive mechanisms. In all three studies, more complex, advanced ToM tasks were employed to avoid ceiling effects. Study I was aimed at investigating if cognitive and affective ToM continues to develop in adolescence and at exploring if basic cognitive variables such as verbal ability, speed of processing, and working memory capacity underlie such development. Hence, two groups of adolescents and young adults completed tasks of ToM and basic cognitive abilities. Large age effects were revealed on both measures of ToM: adolescents performed lower than adults. These age differences remained significant after controlling for basic cognitive variables. However, verbal ability covaried with performance in affective ToM. Overall, results support the hypothesis of an ongoing development of ToM from adolescence to adulthood on both cognitive and affective aspects. Results may further indicate verbal ability being a basic cognitive mechanism of affective ToM. Study II was designed to further explore if affective ToM, as measured with a dynamic realistic task, continues to develop across adolescence. Importantly, this study sought to explore executive functions as higher cognitive mechanisms of developing affective ToM across adolescence. A large group spanning adolescents and young adults evaluated affective mental states depicted by actors in video clips. Additionally, participants were examined with three subcomponents of executive functions, inhibition, updating, and shifting following the classification of Miyake et al. (2000). Affective ToM performance was positively related to age and all three executive functions. Specifically, inhibition explained the largest amount of variance in age related differences of affective ToM performance. Overall, these results indicate the importance of inhibition as key underlying mechanism of developing an advanced affective ToM in adolescence. Study III set out to explore the functional brain development of affective ToM in adolescence by using functional magnetic resonance imaging (fMRI). The affective ToM measure was the behavioral developmentally sensitive task from study II. An additional control condition consisted of the same emotional stimuli with the instruction to focus on physical information. This study faced methodical challenges of developmental fMRI studies by matching performance of groups. The ventromedial prefrontal cortex (vMPFC) was significantly less deactivated in adolescents in comparison to adults, which might suggest that adolescents seem to rely more on self-referential processes for affective ToM. Furthermore, adolescents compared to adults showed greater activation in the dorsolateral prefrontal cortex (DLPFC) in the control condition, indicating that adolescents might be distracted by the emotional content and therefore needed to focus more on the physical content of the stimulus. These findings suggest affective ToM continues to develop on the functional brain level and reveals different underlying neurocognitive strategies for adolescents in contrast to adults. In summary, the current thesis investigated whether ToM continues to develop in adolescence until young adulthood and explored underlying (neuro)cognitive mechanisms. Findings suggest that there is indeed an ongoing development of both the cognitive and affective aspect of ToM, which importantly contributes to the conceptual debate. Moreover, the second benefit to the debate is to demonstrate how this change may occur. As a basic cognitive mechanism verbal ability and as an executive functioning mechanism inhibition was revealed. Furthermore, neurocognitive mechanisms in form of different underlying neurocognitive strategies of adolescents compared to adults were shown. Taken together, ToM development in adolescence seems to mirror a different adaptive cognitive style in adolescence (Crone & Dahl, 2012). This seems to be important for solving the wealth of socio-emotional developmental tasks that are relevant for this age span.:Abstract 1 1 General Introduction 4 1.1 Concept of ToM: cognitive and affective aspects 7 1.2 ToM Development 8 1.2.1 ToM Development until Adolescence 9 1.2.2 ToM Development in Adolescence 12 1.3 Cognitive Mechanisms 14 1.3.1 Basic Cognitive Functions 15 1.3.2 Executive Functions 17 1.4 Neurocognitive Mechanisms 19 1.4.1 Functional brain development of ToM 20 1.4.2 Integrating behavioral and functional brain studies 21 2 Outline and Central Questions 24 2.1 Does ToM continue to develop in adolescence? 24 2.1.1 Does ToM continue to develop on the behavioral level? 24 2.1.2 Does ToM continue to develop on the level of brain function? 25 2.2 What are (neuro)cognitive mechanisms of ToM development in adolescence? 26 2.2.1 What are basic cognitive and executive functioning mechanisms? 26 2.2.2 Can mechanisms be concluded from the integration of behavioral data and functional brain processes? 26 3 Study I – ToM Development in Adolescence and its Basic Cognitive Mechanisms 28 3.1 Introduction 28 3.2 Method 32 3.2.1 Participants 32 3.2.2 Materials 33 3.3 Results 36 3.3.1 Age Effects 36 3.3.2 Influence of puberty on social cognition 37 3.3.3 Controlling for Basic Cognitive Abilities 39 3.4 Discussion 40 3.4.1 Overview 40 3.4.2 Age differences in social cognition 40 3.4.3 Influence of puberty on social cognition 42 3.4.4 Covariates of age differences in social cognition 42 3.4.5 Conclusions 43 4 Study II – ToM Development in Adolescence and its Executive Functioning Mechanisms 45 4.1 Introduction 45 4.2 Method 49 4.2.1 Participants 49 4.2.2 Materials 49 4.3 Results 52 4.3.1 Decomposing the Age Effect in Affective Theory of Mind 54 4.4 Discussion 55 4.4.1 Overview 55 4.4.2 Conclusions 57 5 Study III – ToM Development in Adolescence and its Neurocognitive Mechanisms 59 5.1 Introduction 59 5.2 Method 61 5.2.1 Participants 61 5.2.2 Stimuli, design and procedure 62 5.2.3 Statistical analysis of behavioral data 65 5.2.4 Functional imaging 65 5.2.5 Statistical analysis of fMRI data 66 5.3 Results 67 5.3.1 Behavioral results 67 5.3.2 fMRI results 68 5.4 Discussion 71 5.4.1 Developmental differences in brain activations 71 5.4.2 Conclusions 74 6 General Discussion 75 6.1 Summary of empirical findings 75 6.2 Discussion and integration of the main empirical findings 76 6.2.1 Continued ToM development in adolescence 76 6.2.2 (Neuro)cognitive mechanisms of ToM development in adolescence 80 6.3 Implications and outlook 89 6.3.1 Current findings and their conceptual fit to present models of ToM 90 6.3.2 Underpinning the concept of cognitive and affective ToM 91 6.3.3 Conceptual and methodical implications of performance matching 92 6.3.4 The role of puberty on ToM 94 6.3.5 Predicting other’s economic behavior 95 6.3.6 Structural brain development 96 6.3.7 Applied perspective 97 6.4 Summary 98 References 99