Teses / dissertações sobre o tema "Transfert pavlovian à instrumental"

The current research aimed to further current knowledge on the psychological processes that underpin human outcome-selective Pavlovian-instrumental transfer (PIT) effects. PIT reflects the capacity of a Pavlovian stimulus to selectively potentiate an instrumental response that predicts a common rewarding outcome. PIT effects are often suggested to reflect a relatively automatic S-O-R mechanism, where the stimulus activates the sensory properties of the outcome, which then automatically triggers associated instrumental responses. The current research tested this S-O-R account of PIT against a propositional expected utility theory, which suggests that PIT effects reflect verbalizable inferences about the probability and value of each outcome. Chapter 1 reviews the relevant literature. Chapters 2-4 then report 11 experiments that aimed to set the S-O-R and propositional theories against one another. In Chapter 2, two experiments demonstrated that PIT is sensitive to a reversal instruction (Experiment 2), but is robust against a time pressure (Experiment 1) and concurrent load (Experiment 2) manipulation. Chapter 3 details the development of a novel outcome devaluation procedure, and reports four experiments that examined the effect of both outcome devaluation and verbal instructions on PIT. These experiments demonstrated that a typical PIT procedure produces PIT effects that are insensitive to a very strong devaluation manipulation. Furthermore, PIT effects were observed for a devalued outcome even when an S-O-R mechanism was unlikely to control behaviour. Chapter 4 reports five experiments that show that PIT is highly sensitive to outcome devaluation when multiple outcomes and responses are cued on every transfer test trial. Chapter 5 therefore concludes that, on balance, the results provide converging support for the propositional expected utility theory of PIT.

In Pavlovian conditioning subjects learn the predictive relation between a conditioned stimulus (CS) and a motivationally significant unconditioned stimulus (US), while in instrumental conditioning subjects learn the predictive relation between their responses and a motivationally significant outcome. Both types of associative learning interact in the phenomenon known as the Pavlovian-to-instrumental transfer (PIT) effect. In a PIT procedure subjects received Pavlovian conditioning, in which different CSs are paired with different outcomes (CS1→O1; CS2→O2, etc), and instrumental training, in which each of different responses are paired with these outcomes (R1→O1; R2→O2, etc). After this training the CSs are presented while subjects have the opportunity to perform the instrumental responses. Studies have found that the CS presentations affect instrumental performance by elevating the rate of responding, and this effect can take two different forms: general and specific. In general PIT, Pavlovian cues elevate performance of any instrumental responses that have been trained with a reinforcer of a similar motivational valence to the US. But in the specific PIT effect a CS paired with a particular outcome selectively elevates instrumental responses that produce that outcome, compared to its effect on responses producing different outcomes, i.e. CS1: R1 > R2; CS2: R2 > R1. Different mechanisms have been proposed to explain the specific form of the PIT effect but none of these accounts can explain all the evidence that has been found. Some of these mechanisms propose that at test a CS evokes a representation of the outcome that, in turn, elicits those responses trained with that outcome. In contrast, other accounts suggest that the CS elicits responding via a direct association formed during training. The experiments reported in this thesis were conducted to provide further evidence on this phenomenon in order to distinguish between these mechanisms. The experiments presented here used a standard PIT task with humans as participants. In the Pavlovian phase participants received presentations of different neutral fractal images (CSs), which were paired with presentations of drink and food images (outcomes). In the instrumental phase participants had to press two keys on a computer keyboard (instrumental responses), which were reinforced with the outcomes. The specific PIT effect was measured in a test in which participants could perform both instrumental responses in the presence and absence of the Pavlovian cues. The experiments reported in Chapter 2 and 3 made use of a procedure known as conditioned inhibition, in which a conditioned inhibitor (CI) is trained to signal the absence of an expected outcome; it has been proposed that presentations of a CI suppress the activation of an outcome representation. In the experiments presented in Chapter 2 two CIs were established, one for each of the outcomes, while in those reported in Chapter 3 only one CI was trained. In the studies of both chapters the effect of the CIs, both alone and in compound with excitatory CSs, on the specific PIT effect was assessed. The findings revealed that the CIs did not exert any measurable effect when they were presented alone, but they reduced the specific PIT effect produced by the excitatory CSs. In Chapter 4 CSs were trained in either a forward or backward relation with the outcomes and their effect on instrumental performance was also measured. In some of the experiments the CSs trained in a backward relation with the outcome produced the specific PIT effect, while in others they did not. The contributions of both backward and forward associations were also assessed, and the results suggest that only the forward association supported the specific PIT effect. Overall, the findings suggest that the specific PIT effect is mediated by the activation of an outcome representation, although some assumptions are needed in order to explain the data with extant accounts of PIT.

Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.

In the service of their basic needs and desires, animals and humans can use information from their environment to guide their choice between actions. In the laboratory, the ability for reward-predictive cues to control action selection is studied through outcome-specific Pavlovian-instrumental transfer (PIT-S), in which a stimulus associated with a particular outcomes biases choice between actions towards the response that earned that same outcome. This thesis investigates the determinants of PIT-S within the nucleus accumbens shell (NAc-S), which is selectively recruited to mediate PIT-S, and is not involved in encoding Pavlovian or instrumental associations. Previous work indicated that delta-opioid receptor (DOR) accumulation at the membrane of cholinergic interneurons (CIN-m) in the NAc-S is triggered during Pavlovian learning, and is positively correlated with PIT-S performance. We took three approaches to investigating the role of DOR accumulation: behavioural and pharmacological manipulation of established receptor accumulation, and chemogenetic manipulation of CINs and the afferents that likely utilize DOR accumulation within the NAc-S to mediate PIT-S. Manipulations of the predictive status of Pavlovian cues that abolished PIT-S failed to reverse established DOR accumulation, suggesting that a region that encodes this information controls the use of DOR accumulation to drive PIT-S. Specific pharmacological internalisation of DOR transiently reduced receptor expression on CIN-m in the NAc-S, indicating that CINs have `memory' for DOR accumulation. PIT-S performance was impaired during the period of DOR reduction, indicating that DOR accumulation on NAc-S CIN-m is necessary, but not sufficient, for PIT-S expression. Inactivation of CINs and BLA terminals within the NAc-S impaired and attenuated PIT-S, respectively. Both contralateral and ipsilateral BLA terminal disconnection from CINs in the NAc-S impaired PIT-S performance, despite ipsilateral BLA-NAc-S disconnection failing to affect PIT-S in previous studies, which complicates our ability to interpret this finding. These findings, considered together, suggest that DOR accumulation on CIN-m is necessary, but not sufficient, for PIT-S, and that a functional circuit between BLA terminals and CINs mediates PIT-S, via DOR accumulation on CIN-m.

The ability to adapt to a changing environment requires the ability to extract predictive information to guide future action. Predictive information regarding the relationship between the performance of an action, or some external stimulus, and the delivery of a rewarding outcome can influence behaviour. Additionally, these processes can interact; reward-predictive stimuli can influence action-selection and guide choice, effects that can be examined in the laboratory using tests of Pavlovian-instrumental transfer (PIT). In these tests, a stimulus associated with a specific outcome biases action-selection towards actions previously been associated with that same outcome (specific transfer – sPIT) whereas a stimulus predicting an outcome not earned by any action can increase the vigour of instrumental responding (general transfer – gPIT). This thesis examines the psychological and neural processes that underlie the expression of PIT in humans. Although extensive research in rodents has attempted to clarify the mechanism through which independently trained Pavlovian stimuli are able to influence action, and the neural circuitry involved in the expression of this effect, to date there has been limited research investigating PIT in humans. To address this, a behavioural task adapted from the rodent literature was used to examine the influence of Pavlovian stimuli on both sPIT and gPIT; i.e., on the effects of predictive stimuli on response bias and response vigour in a comparable manner to the established research in rodents.

The extent to which motivational mechanisms contribute to reward seeking processes is crucial to our understanding of certain abnormal behaviours, including addiction. Pavlovian conditioning endows reward-associated stimuli with the ability to modulate goal-directed actions for that same reward (Pavlovian-to-Instrumental transfer; PIT). Learning and motivational theories attempt to describe the processes by which stimuli in the environment acquire incentive properties, attract attention and drive reward-seeking behaviours and bear many resemblances, but there are also important differences. This thesis uses a general PIT model in humans to further our understanding of these discrepancies and investigates the effect mood has on these processes. Firstly, altering the value of the reward affected the rigor of instrumental performance, but the same changes in outcome value did not affect the expectancy of, attention to, or emotional reactivity to the cues suggesting that in Pavlovian learning, apart from the nature of outcomes, the value of outcomes is encoded such that changes in outcome value prevent transfer of a Pavlovian cue's incentive properties to alter goal-directed action. Secondly, the further papers assess the extent to which mood modulates this same action. When under negative mood a general reduction in motivation, driven by an attenuated sensitivity to the reward was observed, as well as a dissociation between aversive and appetitive outcomes. The remaining study explored whether mood altered Pavlovian learning and revealed that those under state negative mood take longer to express their knowledge explicitly and that those under positive mood showed altered attention and emotional responses towards the same stimuli. The approach used in this thesis shows the merits of both motivational and learning theories, and further demonstrates the link between mood and motivation. Additionally, a dissociation between punishment and reward prediction when under negative mood was demonstrated and builds upon this important distinction.

Chaque jour, nous sommes confrontés à de nombreuses décisions qui façonnent nos comportements. Les facteurs influençant ces choix sont multiples. Les besoins et désirs immédiats jouent souvent un rôle important dans la sélection des actions, guidés par la valeur du but. Cependant, il est essentiel de reconnaître l'impact des stimuli environnementaux. Par exemple, les stimuli alimentaires peuvent non seulement nous orienter vers la nourriture, mais aussi déclencher des envies, même en l'absence de faim. Afin d’identifier le rôle du cortex insulaire (CI) du rat dans les actions guidées par des stimuli et visant à obtenir des aliments, nous avons utilisé le paradigme du transfert Pavlovien-Instrumental (PIT). Étant donné le rôle bien établi du CI dans l'encodage et la surveillance des attentes générales et spécifiques, et sa contribution critique dans le choix guidé par la valeur spécifique d’un but, nous avons émis l'hypothèse d'un rôle du CI pendant le test de transfert PIT où les actions sont influencées par des stimuli prédictifs de récompense. Grâce à une approche chimiogénétique, nous avons démontré que l'inhibition du CI pendant les tests de transfert généraux et spécifiques abolissait la capacité des stimuli prédictifs de récompense pavloviens à stimuler la réponse instrumentale et à orienter spécifiquement le choix de l'action vers la même récompense que le stimulus prédictif présenté, respectivement. Ces résultats démontrent pour la première fois le rôle critique du CI dans le choix guidé par stimulus, englobant à la fois les propriétés motivationnelles générales acquises par les stimuli pavloviens et leur capacité à orienter spécifiquement la sélection de l'action vers des résultats spécifiques. De plus, nos résultats préliminaires suggèrent que cette dernière peut dépendre de façon critique d'une voie cortico-thalamique intacte impliquant la partie médiodorsale du thalamus
Every day, individuals are faced with numerous decisions that shape their behavior. The factors influencing these choices are multifaceted and encompass a range of considerations. Immediate needs and desires often play a significant role in action selection, guided by the value of the outcome. However, it is crucial to recognize the impact of environmental stimuli. For instance, stimuli associated with food can not only direct us toward nourishment but also trigger cravings, even in the absence of hunger. To uncover the role of the rat insular cortex (IC) in stimulus-guided actions directed towards obtaining food outcomes, we used the Pavlovian-to-Instrumental Transfer (PIT) paradigm. Given the well-established role of IC in encoding and tracking general and specific outcome-expectancies, and its critical contribution in choice guided by specific-outcome values, we hypothesized a role of the IC during the PIT transfer test where actions are influenced by reward-predictive stimuli. Using chemogenetics, we demonstrated that IC inhibition during both general and specific transfer tests abolished the ability of Pavlovian reward-predictive stimuli to energize instrumental responding, and to specifically bias action selection towards the same outcome as the presented predictive stimulus, respectively. These results demonstrated for the first time the critical role of the IC in stimulus-guided choice, encompassing both the general motivational properties acquired by Pavlovian stimuli and their ability to specifically bias action selection towards specific outcomes. Moreover, preliminary results suggest that the latter may critically depend on an intact cortico-thalamic pathway involving the mediodorsal part of the thalamus. In conclusion, we provide the first evidence that the GC is required for both general and specific forms of PIT, with the latter depending on an intact cortico-thalamic pathway

Die These fasst die ersten Untersuchungen zum Pawlowsch`-Instrumentellen Transfer in alkoholabhängigen (AA) Patienten zusammen. Es ist bekannt, dass kontextuelle Umgebungsreize Verhalten beeinflussen. Tier- und Humanstudien haben gezeigt, dass positive Pawlowsche Reize instrumentelles Antwortverhalten verstärken und negative Pawlowsche Reize dieses reduzieren (PIT-Effekt). Bei Abhängigkeit wird angenommen, dass dieser Mechanismus relevant für Rückfall ist, da z.B. drogenassoziierte Reize bei Patienten im Vergleich zu Kontrollen erhöhtes Verlagen und funktionelle Aktivität in Belohnungsarealen auslösen. In Tier- und Humanstudien wurden stärkere PIT-Effekte vor allem mit funktioneller Aktivierung im Nucleus Accumbens (NAcc) beobachtet. Weiterhin zeigten sich bei Probanden mit stärkerem PIT-Effekt und bei AA Patienten erhöhte Impulsivitätswerte. Die PIT-Aufgabe besteht aus 3 Hauptteilen: i) Instrumentelle Konditionierung, ii) Pawlowsche Konditionierung, iii) Transfer mit Pawlowschen oder alkoholassoziierten Kontextstimuli. Impulsives Auswahlverhalten wurde durch die delay discounting Aufgabe erhoben. Es zeigten sich signifikant stärkere PIT-Effekte mit Pawlowschen Kontextreizen in AA Patienten im Vergleich zu Kontrollen mit funktioneller Aktivierung im NAcc, die zur Rückfallvorhersage beitrug. Der Transfer mit alkoholassoziierten Kontextreizen bewirkte eine signifikante Reduktion des instrumentellen Antwortverhaltens mit neuronalem Korrelat im NAcc nur bei abstinenten Patienten. Impulsives Auswahlverhalten und PIT hingen nur bei Patienten positiv zusammen. Die Studien lassen darauf schließen, dass PIT ein für Rückfall wichtiger Mechanismus ist mit funktionellem Korrelat im NAcc, der sich für motivationale Prozesse als auch als Salienzsignal relevant gezeigt hat. Die Subgruppe von hoch impulsiven Patienten ist im Besonderen durch Kontextreize im instrumentellen Antwortverhalten beeinflussbar, daher sollte ihr besondere Aufmerksamkeit bei Interventionen zukommen.
This thesis summarizes the first Pavlovian-to-instrumental transfer (PIT) studies in alcohol-dependent (AD) patients. Contextual stimuli are known to influence our behavior. Animal and human studies showed that positive Pavlovian stimuli enhance and negative Pavlovian stimuli reduce instrumental behavior (PIT effect). This mechanism might be relevant for relapse risk, as drug-associated stimuli have shown to enhance e.g. craving and functional activation in reward-related brain areas in patients compared to controls. In animal and human studies enhanced PIT effects were associated with activation particularly in the nucleus accumbens (NAcc). Moreover, control subjects with stronger PIT effects and AD patients were more impulsive on different facets of impulsivity. The PIT task consists of three main parts: i) instrumental conditioning, ii) Pavlovian conditioning, iii) transfer with Pavlovian background stimuli and instrumental task in the foreground (nondrug-related PIT: Pavlovian contextual cues; drug-related PIT: alcohol-related contextual cues). Choice impulsivity was measured by delay discounting task. We observed significantly enhanced nondrug-related PIT effects in AD patients compared to controls with a functional activation in the NAcc being predictive for relapse. Regarding drug-related PIT effects, we observed significantly reduced instrumental behavior during alcohol-related backgrounds with neural correlates in the NAcc in abstainers only. Choice impulsivity was positively related to PIT in AD patients only. Our data suggest that PIT is a mechanism contributing to relapse in AD patients with functional correlations within the NAcc, which based on our data is involved in motivation and attribution of salience. The subgroup of high impulsive patients is particularly susceptible for PIT effects, thus should be main target for intervention programs.

This thesis investigates interactions between Pavlovian and instrumental processes. The first chapter provides an evaluation of various theoretical analyses of how these two processes might interact in the context of two types of phenomena: Pavlovian-to-instrumental transfer (PIT) and the renewal of instrumental responses that have been extinguished. It is argued that the conditions under which both phenomena are observed do not sit readily with the theoretical analyses that have been offered for them. Chapter 2 reports three experiments that examined the conditions under which outcome-selective and general PIT occur in rats. Outcome-selective PIT was not increased by procedures that should increase the distinctiveness of the outcomes; but general PIT was more likely to be observed under conditions in which the distinctiveness of the outcomes should be low (Experiments 1-3). Chapter 3 contrasted the standard stimulus-outcome-response analysis of outcome-selective PIT with a novel theoretical analysis based on mediated stimulus-response associations that directly affect test performance (i.e., without the outcome becoming activated during the test). Experiment 4 demonstrated an outcome-selective PIT effect when the outcome (O) was embedded in the Pavlovian conditioned stimulus (S), and Experiments 5 and 6 showed that outcome-selective PIT was more likely to be observed after backward pairings (i.e., O-S) than after forward pairings (i.e., S-O). These results are consistent with the following analysis: Instrumental training establishes response-outcome and outcome-response associations, and during subsequent backward conditioning the outcome provokes its associated instrumental response during the stimulus and thereby allows a stimulus–response association to be acquired. This stimulus-response association then directly generates outcome-selective PIT at test. Experiment 7 provided direct evidence to support the ix assumptions upon which this analysis relies. These results, together with other paradoxical effects of the Pavlovian relationship, are incongruent with accounts of outcome-selective PIT that rely on a stimulus-outcome-response chain. Chapter 4 explored another instance where Pavlovian stimuli exert a powerful influence on instrumental performance: the case of instrumental renewal. Two fundamental issues were addressed: whether or not direct Pavlovian associations are responsible for the renewal effect, and whether or not renewed responses are controlled by goal-directed processes or stimulus-response associations. In Experiment 8, instrumental renewal was observed without concomitant involvement of any excitatory or inhibitory Pavlovian properties of the contexts involving the outcome; and in Experiment 9, renewed responding was sensitive to the current value of the outcome. Taken together, these results suggest that the extinction context exerts a direct (or hierarchical) inhibitory influence on the instrumental response-outcome association, the removal of which allows the impact of the response-outcome association of performance to be revealed. Chapter 5 explores the broader implications of these results for current theoretical analyses that rely on the idea that Pavlovian and instrumental processes interact through shared access to the features of the outcome.

Pesquisas com drogas de abuso têm mostrado consistentemente que a apresentação de estímulos ambientais associados ao uso destas substâncias pode induzir comportamentos de busca e autoadministração das mesmas. Existe a hipótese de que o controle que estímulos ambientais adquirem sobre comportamentos de autoadministração e busca por drogas de abuso poderia ser influenciado tanto pela forma de administração da droga, autoadministração (administração ativa) ou heteroadministração (administração passiva), quanto pela contingência (operante ou respondente) em que a droga foi associada com tais estímulos. Foram formados trios compostos por um sujeito de cada grupo (CONT, ACOP e VEÍC) e realizados dois experimentos. Inicialmente os sujeitos de cada trio foram acoplados por meio de caixas experimentais separadas e expostos a tentativas discretas de apresentação dos estímulos luminosos, S1 e S2, simultaneamente. Como consequência do girar a roda operante na presença de S1 por um integrante do grupo CONT, este recebia uma infusão endovenosa de morfina (0,75 mg/kg), e simultaneamente os animais acoplados no trio recebiam uma infusão de morfina na mesma dose (grupo ACOP) ou de veículo (grupo VEÍC). Posteriormente, os sujeitos de todos os grupos foram treinados a pressionar uma barra por infusões endovenosas de morfina, sem contingência discriminativa programada alguma. Para esta fase, no experimento 1, S2 esteve presente durante as sessões experimentais, porém no experimento 2, nenhum S foi apresentado. Finalmente, os estímulos S1 e S2 foram apresentados em tentativas discretas, em condições de extinção. Os resultados mostram que, durante a extinção, o desempenho dos animais do grupo CONT, mas não os dos grupos ACOP e VEÍC, foi condizente com o treino recebido inicialmente (com 80% ou mais de respostas na barra em presença de S1), indicando que foi estabelecido controle discriminativo sobre a autoadministração de morfina no treino sob a contingência operante, mas não sob a respondente. Estes resultados sugerem que comportamentos de autoadministração e busca por drogas de abuso são influenciados tanto pela forma de administração da droga, quanto pelo tipo de contingência em que uma droga é associada com estímulos ambientais
Drug abuse research has consistently shown that presentation of a drug associated with environmental stimuli can induce drug-seeking and drug-administration behaviors. It has been hypothesized that stimuli control over drug-seeking and self-administration behaviors could be influenced by drug administrations nature, self-administration (active administration) or hetero-administration (passive administration), and also influenced by the drug-stimuli association contingency (operant or respondent). Animals were exposed to right jugular vein catheterization procedure. Groups Contingent (C), Yoked (Y) and Toked Saline (YS) were formed randomly after recovery. Yoked triads were formed with one subject from each group and two experiments were executed. Initially a discriminative training (light stimuli S1 and S2 discrete trials) was presented to triads. Each time C S group member turned an instrumental wheel in presence of S1, simultaneously, an intravenous morphine infusion (0.75 mg/kg) were administrated to that subject and yoked Y group member, as well as an intravenous saline infusion was administrated to yoked YS group member, in every triad. Afterward all subjects were individually trained to lever-press for an intravenous morphine infusion with no discrimination contingency programed. In this phase, S2 was presented through sessions in Experiment 1, while in Experiment 2 no S were presented. After achieving response stability, subjects were exposed to extinction sessions. Stimuli S1 and S2 discrete trials were presented but no consequences were programed for bar-press responses. Results show that only C groups performance was consistent with the previously received discriminative training (80% or more of bar-press responses in S1 presence) during extinction sessions, indicating that an operant training, but not a respondent training, successfully established morphine self-administration discriminative control. These results suggest that self-administration behaviors are in fact influenced by drugs administration nature and also by the drug-stimuli association contingency

Ghrelin is an orexigenic peptide that binds to the growth hormone secretagogue receptor (GHS-R). While it is known for regulating homeostatic feeding, recent research has revealed a role for ghrelin in reward-seeking. Missing from this research, however, is a systematic investigation into the role of ghrelin in reward-seeking: it is unclear whether ghrelin provides a reward signal, energises instrumental actions that earn palatable foods, or affects the ability of Pavlovian food-paired cues or food itself to invigorate instrumental responding, either generally or through the retrieval of specific associations. Given these phenomena promote overeating and weight gain, this thesis examined the role of ghrelin in Pavlovian and instrumental learning and performance. Overall, it was found that while ghrelin does not participate in Pavlovian or instrumental learning, it does modulate effort/response vigour: GHS-R antagonism attenuated established instrumental and progressive ratio responding for palatable food in rats. GHS-R antagonism had no effect on outcome devaluation, confirming that ghrelin affects instrumental responding by modulating effort/response vigour and not a change in outcome value. GHS-R antagonism had no effect on the return of responding driven by re-exposure to food after extinction (outcome-induced and outcome-specific reinstatement), and attenuated the general but not specific form of Pavlovian-instrumental transfer (PIT). Thus, ghrelin is also involved in the ability of Pavlovian food-paired cues to enhance instrumental responding based on a general excitatory relationship with food reward. As ghrelin levels fluctuate with changes in hunger/satiety, this thesis also investigated whether changes in ghrelin signalling recapitulate the effects of hunger/satiety. Generally, satiety had similar effects but was a more consistent modulator of instrumental performance and general PIT.

Diese Dissertation fasst drei wissenschaftliche Arbeiten (Artikel) zusammen, welche sich mit veränderten Entscheidungsprozessen bei substanzgebundenen- und substanzungebundenen Abhängigkeitserkrankungen beschäftigen. In Artikel I wurde beobachtet, dass Probanden mit Alkoholkonsumstörung (AD) und Probanden mit Glücksspielstörung (GD) eine ähnlich reduzierte Verlustaversion gegenüber gesunden Kontrollen (HC) aufweisen. Beide Gruppen zeigten jedoch unterschiedliche neuronale Korrelate dieser reduzierten Verlustaversion: Während AD-Probanden eine unterschiedliche funktionelle Aktivität im dorsal-lateralen-präfrontalen Kortex im Vergleich zu HC aufwiesen, zeigten GD-Probanden eine veränderte funktionelle Konnektivität zwischen Amygdala und orbito-frontalem Kortex (OFC) bzw. medial-präfrontalem Kortex. In den Artikeln II und III wurde untersucht, ob das Verhalten und die neuronale Aktivität bei einer Verlustaversionsaufgabe bei GD-Probanden moduliert wird, wie dies in ähnlichen Studien bei AD-Probanden beobachtet wurde. Tatsächlich konnten GD-Probanden von HC-Probanden auf Grundlage ihrer veränderten Glücksspielannahme während der Präsentation spielbezogener Hinweisreize unterschieden werden. Auf neuronaler Ebene (Artikel III) konnten GD-Probanden von HC-Probanden durch die neuronalen Korrelate der reizinduzierten Veränderungen im Spielverhalten in einem Netzwerk aus Amygdala, Nucleus Accumbens und OFC unterschieden werden. Da in den Studien der Fokus auf Glücksspielabhängigkeit lag, also auf einer Abhängigkeit, welche unabhängig von Substanzmissbrauch existiert, deuten die hier diskutierten Ergebnisse darauf hin, dass verminderte Verlustaversion, sowie erhöhte reizinduzierte Veränderungen im Entscheidungsverhalten – welches beides bekannte Phänomene von Substanzabhängigkeiten sind – nicht durch Substanzmissbrauch zustande kommen. Beide Phänomene scheinen vielmehr erlernte Merkmale oder sogar prädisponierende Faktoren von Abhängigkeitserkrankungen zu sein.
This dissertation summarizes three papers concerned with decision-making impairments in a substance-based and a non-substance-based addictive disorder. In Paper I, it was observed that subjects with alcohol use disorder (AD) and subjects with gambling disorder (GD) show similarly reduced loss aversion. Both groups, however, showed different neural correlates of this reduced loss aversion: While AD subjects showed different functional activity in dorsal-lateral-prefrontal cortex compared to healthy controls (HC), GD subjects showed different amygdala-orbital-frontal and amygdala-medial-prefrontal connectivity. Paper II and III investigated whether behavior and neural activity in a loss aversion task is modulated in GD subjects, as has been observed in similar studies in AD subjects. The data showed that GD subjects can be distinguished from HC subjects using a behavioral pattern of increased cue-induced gamble increase when gambling-related cues are presented in the background. On neural level (Paper III), GD subjects could be distinguished from HC subjects by neural correlates of cue-induced changes in gambling behavior in a network of amygdala, nucleus accumbens and orbital-frontal cortex. Since the focus of the studies was GD, an addiction that is independent of substance abuse, the results suggest that reduced loss aversion and increased cue-induced changes in gambling behaviors, two phenomena related to substance-based addictions, are not dependent on a substance of abuse but rather on learned characteristics or even on predisposing traits of addictive disorders.

Le conditionnement Pavlovien, l'acquisition de réponses vers des stimuli neutres associés à des récompenses, et le conditionnement instrumental, l'expression de comportements pour atteindre des buts, sont au cœur de nos capacités d'apprentissage. Ils sont souvent étudiés séparément malgré les preuves de leur enchevêtrement. Les modèles de conditionnement instrumental reposent sur le formalisme de l'apprentissage par renforcement (RL), alors que les modèles du conditionnement Pavlovien reposent surtout sur des architectures dédiées souvent incompatibles avec ce formalisme, compliquant l'étude de leurs interactions.Notre objectif est de trouver des concepts, qui combinés à des modèles RL puissent offrir une architecture unifiée permettant une telle étude. Nous développons un modèle qui combine un système RL classique, qui apprend une valeur par état, avec un système RL révisé, évaluant les stimuli séparément et biaisant le comportement vers ceux associés aux récompenses. Le modèle explique certaines réponses inadaptées par l'interaction néfaste des systèmes, ainsi que certaines différences inter-individuelles par une simple variation au niveau de la population de la contribution de chaque système dans le comportement global.Il explique une activité inattendue de la dopamine, vis-à-vis de l'hypothèse qu'elle encode un signal d'erreur, par son calcul sur les stimuli et non les états. Il est aussi compatible avec une hypothèse alternative que la dopamine contribue aussi à rendre certains stimuli recherchés pour eux-mêmes. Le modèle présente des propriétés prometteuses pour l'étude du conditionnement Pavlovien,du conditionnement instrumental et de leurs interactions
Pavlovian conditioning, the acquisition of responses to neutral stimuli previously paired with rewards, and instrumental conditioning, the acquisition of goal-oriented responses, are central to our learning capacities. However, despite some evidences of entanglement, they are mainly studied separately. Reinforcement learning (RL), learning by trials and errors to reach goals, is central to models of instrumental conditioning, while models of Pavlovian conditioning rely on more dedicated and often incompatible architectures. This complicates the study of their interactions. We aim at finding concepts which combined with RL models may provide a unifying architecture to allow such a study. We develop a model that combines a classical RL system, learning values over states, with a revised RL system, learning values over individual stimuli and biasing the behaviour towards reward-related ones. It explains maladaptive behaviours in pigeons by the detrimental interaction of systems, and inter-individual differences in rats by a simple variation at the population level in the contribution of each system to the overall behaviour. It explains unexpected dopaminergic patterns with regard to the dominant hypothesis that dopamine parallels a reward prediction error signal by computing such signal over features rather than states, and makes it compatible with an alternative hypothesis that dopamine also contributes to the acquisition of incentive salience, making reward-related stimuli wanted for themselves. The present model shows promising properties for the investigation of Pavlovian conditioning, instrumental conditioning and their interactions

Le conditionnement Pavlovien, l'acquisition de réponses vers des stimuli neutres associés à des récompenses, et le conditionnement instrumental, l'expression de comportements pour atteindre des buts, sont au cœur de nos capacités d'apprentissage. Ils sont souvent étudiés séparément malgré les preuves de leur enchevêtrement. Les modèles de conditionnement instrumental reposent sur le formalisme de l'apprentissage par renforcement (RL), alors que les modèles du conditionnement Pavlovien reposent surtout sur des architectures dédiées souvent incompatibles avec ce formalisme, compliquant l'étude de leurs interactions.Notre objectif est de trouver des concepts, qui combinés à des modèles RL puissent offrir une architecture unifiée permettant une telle étude. Nous développons un modèle qui combine un système RL classique, qui apprend une valeur par état, avec un système RL révisé, évaluant les stimuli séparément et biaisant le comportement vers ceux associés aux récompenses. Le modèle explique certaines réponses inadaptées par l'interaction néfaste des systèmes, ainsi que certaines différences inter-individuelles par une simple variation au niveau de la population de la contribution de chaque système dans le comportement global.Il explique une activité inattendue de la dopamine, vis-à-vis de l'hypothèse qu'elle encode un signal d'erreur, par son calcul sur les stimuli et non les états. Il est aussi compatible avec une hypothèse alternative que la dopamine contribue aussi à rendre certains stimuli recherchés pour eux-mêmes. Le modèle présente des propriétés prometteuses pour l'étude du conditionnement Pavlovien,du conditionnement instrumental et de leurs interactions
Pavlovian conditioning, the acquisition of responses to neutral stimuli previously paired with rewards, and instrumental conditioning, the acquisition of goal-oriented responses, are central to our learning capacities. However, despite some evidences of entanglement, they are mainly studied separately. Reinforcement learning (RL), learning by trials and errors to reach goals, is central to models of instrumental conditioning, while models of Pavlovian conditioning rely on more dedicated and often incompatible architectures. This complicates the study of their interactions. We aim at finding concepts which combined with RL models may provide a unifying architecture to allow such a study. We develop a model that combines a classical RL system, learning values over states, with a revised RL system, learning values over individual stimuli and biasing the behaviour towards reward-related ones. It explains maladaptive behaviours in pigeons by the detrimental interaction of systems, and inter-individual differences in rats by a simple variation at the population level in the contribution of each system to the overall behaviour. It explains unexpected dopaminergic patterns with regard to the dominant hypothesis that dopamine parallels a reward prediction error signal by computing such signal over features rather than states, and makes it compatible with an alternative hypothesis that dopamine also contributes to the acquisition of incentive salience, making reward-related stimuli wanted for themselves. The present model shows promising properties for the investigation of Pavlovian conditioning, instrumental conditioning and their interactions

Les modulateurs electro-optiques (EOM) sont des composants importants dans les systemes de telecommunication. Malheureusement, ils ne sont pas parfaitement stables dans Ie temps et leur fonction de transfert (TF) a tendance a se decaler durant Ie temps d'operation. La derive de la TF d'un EOM peut etre expliquee par des effets differents tels que les changements de la temperature ambiante, de la polarisation ou de l'efficacite de couplage optique. La these presente une methode de me sure de la derive de la TF de I'EOM (a grace d'estimation du comportement non-linearite du modulateur, NLl), et propose deux systemes instrumentaux pour ameliorer son fonctionnement: Ie premier pour contraler la temperature de l'EOM, il est possible de forcement reduire cette derive, Ie deuxieme pour compenser la derive (la stabilisation du point de fonctionnement autour du point quadrature est obtenue jusqu'au 0,22% ou la fluctuation de phase est de 0,44°). Ces techniques ont ete aussi appliquees pour ameliorer Ie comportement d'un oscillateur optoelectronique haute frequence. Nous avons realise les experiences par asservissement de temperature, par compensation de la derive. Pour une stabilite de I'OEO a court terme, la stabilisation de la frequence est amelioree jusqu'a 28% en utilisant un contrale de temperature seule etjusqu'a 71 % avec les deux processus. Pour une stabilite de l'OEO a long terme, en deux cas sans contra Ie, I'OEO fonctionne pendant 3 heures et pendant 1,6 heure (puis I'OEO ne marche plus). En utilisant une compensation de la derive de la TF de I'EOM, l'OEO fonctionne bien meme apres 7 heures et 8 heures.

Dysfunktionale Lernvorgänge (wie z.B. Pawlowsche Konditionierung) können bei Patienten mit Alkoholabhängigkeit das Rückfallrisiko erhöhen, was innerhalb der vorliegenden Arbeit mittels drei Studien untersucht wurde.

Dissertação de mestrado em Ciências da Saúde
Exposure to early life stress (ELS) or elevated levels of glucocorticoids (GC) has an enduring effect in the central nervous system (CNS), which can lead to maladaptive behaviour in adult life. Several studies suggest that ELS increases the vulnerability to develop psychiatric disorders, such as schizophrenia, depression or addiction. Synthetic GCs such as dexamethasone (DEX) are frequently prescribed in clinics, to ensure foetal lung maturation in preterm risk pregnancies. Despite its beneficial effects in the lungs, it has been shown that GCs can lead to long-lasting effects on brain function. Interestingly, neuronal dopamine (DA) populations seem to be particularly vulnerable to elevated levels of GCs. For example, adult rats exposed in utero to GC (iuGC) showed significant alterations in DAergic reward mesolimbic circuit, namely in the ventral tegmental area (VTA), nucleus accumbens (NAcc) and amygdala, alterations that occurred in parallel with increased drug-seeking behaviour. To further assess the integrity of the reward circuitry in iuGC animals, we decided to analyse their performance in the Pavlovian-to-instrumental (PIT) test, a paradigm that involves the ability of environmental stimuli to activate the memory of sensory-specific features of the outcome/reward used in instrumental conditioning. Interestingly, iuGC animals were impaired in both non-selective and selective protocols of PIT. Since PIT performance strongly depends on prefrontal cortex (PFC), we decided to perform a morphometric analysis of this brain region. iuGC treatment induced significant changes in the volume, cell numbers and neuronal morphology of the medial PFC and less so on the orbitofrontal cortex. Molecular analysis of these brain regions further revealed alterations on the expression levels of dopamine receptors (Drd) 1 and 2 and in molecules important for neuronal remodelling. Altogether, our results suggest that iuGC exposure alters the reward circuitry, impairing PIT performance. This reduction in the incentive salience attributed to cues predicting natural rewards can ultimately contribute for an increased vulnerability for non-natural rewards, and eventually explain the observed increased sensitivity and preference to drugs of abuse.
A exposição a stress pré-natal (SPN) ou a níveis elevados de glucocorticóides (GC), tem um impacto duradouro no sistema nervoso central (SNC), o que pode levar a alterações comportamentais na vida adulta. Vários estudos sugerem que o SPN aumenta a vulnerabilidade para o desenvolvimento de doenças psiquiátricas, tais como a esquizofrenia, depressão ou adição. GCs sintéticos como a dexametasona (DEX) são frequentemente prescritos na prática clínica, para assegurar maturação pulmonar fetal em situações de gravidez com risco de parto pré-termo. Apesar dos efeitos benéficos nos pulmões, vários estudos apontam para um efeito deletério no SNC. Curiosamente, as populações neuronais dopaminérgicas parecem ser particularmente vulneráveis a elevados níveis de GCs. Por exemplo, ratos adultos expostos in utero a GCs (iuGC) exibem alterações significativas no circuito dopaminérgico de recompensa – a via mesolimbica, nomeadamente na área tegmental ventral, no núcleo accumbens e amígdala; alterações essas associadas a um aumento de vulnerabilidade para drogas de abuso. A fim de avaliar a integridade do sistema de recompensa, analisamos a performance dos animais iuGC no teste Pavlovian-to-instrumental (PIT) transfer, que é um paradigma que envolve a capacidade de estímulos ambientais ativarem a memória de características sensoriais de recompensa no condicionamento instrumental. Uma vez que o PIT depende em grande parte do córtex pré-frontal (PFC), decidimos analisar esta região a nível estereológico e morfológico. Verificamos que a exposição a iuGC induz alterações significativas no volume, número de células e morfologia do PFC medial, com menor impacto no córtex orbitofrontal. Análise molecular destas regiões revelou ainda alterações na expressão dos receptores de dopamina 1 e 2, e de moléculas importantes para a remodelação neuronal. De uma forma global, os nossos resultados sugerem que exposição a iuGC altera o sistema de recompensa, inibindo a performance do PIT. Esta redução na motivação atribuída a pistas que predizem recompensas naturais pode, em último caso, contribuir para uma vulnerabilidade acrescida para recompensas não-naturais (drogas), e eventualmente explicar o aumento da sensibilização e preferência para drogas de abuso observada nestes animais.