Adaptive and Maladaptive Implications of Reinforcement Learning Processes: Fronto-Striatal Loops and Behavioural Correlates

That humans and animals learn from interaction with the environment is a foundational idea underlying nearly all theories of learning and intelligence. Learning that certain outcomes are associated with specific actions or stimuli (both internal and external), is at the very core of the capacity to adapt behaviour to environmental changes. In the present work, appetitive and aversive reinforcement learning paradigms have been used to investigate the fronto-striatal loops and behavioural correlates of adaptive and maladaptive reinforcement learning processes, aiming to a deeper understanding of how cortical and subcortical substrates interacts between them and with other brain systems to support learning. By combining a large variety of neuroscientific approaches, including behavioral and psychophysiological methods, EEG and neuroimaging techniques, these studies aim at clarifying and advancing the knowledge of the neural bases and computational mechanisms of reinforcement learning, both in normal and neurologically impaired population.

Essays on the political economy of European integration

Recently, a rising interest in political and economic integration/disintegration issues has been developed in the political economy field. This growing strand of literature partly draws on traditional issues of fiscal federalism and optimum public good provision and focuses on a trade-off between the benefits of centralization, arising from economies of scale or externalities, and the costs of harmonizing policies as a consequence of the increased heterogeneity of individual preferences in an international union or in a country composed of at least two regions. This thesis stems from this strand of literature and aims to shed some light on two highly relevant aspects of the political economy of European integration. The first concerns the role of public opinion in the integration process; more precisely, how economic benefits and costs of integration shape citizens' support for European Union (EU) membership. The second is the allocation of policy competences among different levels of government: European, national and regional. Chapter 1 introduces the topics developed in this thesis by reviewing the main recent theoretical developments in the political economy analysis of integration processes. It is structured as follows. First, it briefly surveys a few relevant articles on economic theories of integration and disintegration processes (Alesina and Spolaore 1997, Bolton and Roland 1997, Alesina et al. 2000, Casella and Feinstein 2002) and discusses their relevance for the study of the impact of economic benefits and costs on public opinion attitude towards the EU. Subsequently, it explores the links existing between such political economy literature and theories of fiscal federalism, especially with regard to normative considerations concerning the optimal allocation of competences in a union. Chapter 2 firstly proposes a model of citizens’ support for membership of international unions, with explicit reference to the EU; subsequently it tests the model on a panel of EU countries. What are the factors that influence public opinion support for the European Union (EU)? In international relations theory, the idea that citizens' support for the EU depends on material benefits deriving from integration, i.e. whether European integration makes individuals economically better off (utilitarian support), has been common since the 1970s, but has never been the subject of a formal treatment (Hix 2005). A small number of studies in the 1990s have investigated econometrically the link between national economic performance and mass support for European integration (Eichenberg and Dalton 1993; Anderson and Kalthenthaler 1996), but only making informal assumptions. The main aim of Chapter 2 is thus to propose and test our model with a view to providing a more complete and theoretically grounded picture of public support for the EU. Following theories of utilitarian support, we assume that citizens are in favour of membership if they receive economic benefits from it. To develop this idea, we propose a simple political economic model drawing on the recent economic literature on integration and disintegration processes. The basic element is the existence of a trade-off between the benefits of centralisation and the costs of harmonising policies in presence of heterogeneous preferences among countries. The approach we follow is that of the recent literature on the political economy of international unions and the unification or break-up of nations (Bolton and Roland 1997, Alesina and Wacziarg 1999, Alesina et al. 2001, 2005a, to mention only the relevant). The general perspective is that unification provides returns to scale in the provision of public goods, but reduces each member state’s ability to determine its most favoured bundle of public goods. In the simple model presented in Chapter 2, support for membership of the union is increasing in the union’s average income and in the loss of efficiency stemming from being outside the union, and decreasing in a country’s average income, while increasing heterogeneity of preferences among countries points to a reduced scope of the union. Afterwards we empirically test the model with data on the EU; more precisely, we perform an econometric analysis employing a panel of member countries over time. The second part of Chapter 2 thus tries to answer the following question: does public opinion support for the EU really depend on economic factors? The findings are broadly consistent with our theoretical expectations: the conditions of the national economy, differences in income among member states and heterogeneity of preferences shape citizens’ attitude towards their country’s membership of the EU. Consequently, this analysis offers some interesting policy implications for the present debate about ratification of the European Constitution and, more generally, about how the EU could act in order to gain more support from the European public. Citizens in many member states are called to express their opinion in national referenda, which may well end up in rejection of the Constitution, as recently happened in France and the Netherlands, triggering a European-wide political crisis. These events show that nowadays understanding public attitude towards the EU is not only of academic interest, but has a strong relevance for policy-making too. Chapter 3 empirically investigates the link between European integration and regional autonomy in Italy. Over the last few decades, the double tendency towards supranationalism and regional autonomy, which has characterised some European States, has taken a very interesting form in this country, because Italy, besides being one of the founding members of the EU, also implemented a process of decentralisation during the 1970s, further strengthened by a constitutional reform in 2001. Moreover, the issue of the allocation of competences among the EU, the Member States and the regions is now especially topical. The process leading to the drafting of European Constitution (even if then it has not come into force) has attracted much attention from a constitutional political economy perspective both on a normative and positive point of view (Breuss and Eller 2004, Mueller 2005). The Italian parliament has recently passed a new thorough constitutional reform, still to be approved by citizens in a referendum, which includes, among other things, the so called “devolution”, i.e. granting the regions exclusive competence in public health care, education and local police. Following and extending the methodology proposed in a recent influential article by Alesina et al. (2005b), which only concentrated on the EU activity (treaties, legislation, and European Court of Justice’s rulings), we develop a set of quantitative indicators measuring the intensity of the legislative activity of the Italian State, the EU and the Italian regions from 1973 to 2005 in a large number of policy categories. By doing so, we seek to answer the following broad questions. Are European and regional legislations substitutes for state laws? To what extent are the competences attributed by the European treaties or the Italian Constitution actually exerted in the various policy areas? Is their exertion consistent with the normative recommendations from the economic literature about their optimum allocation among different levels of government? The main results show that, first, there seems to be a certain substitutability between EU and national legislations (even if not a very strong one), but not between regional and national ones. Second, the EU concentrates its legislative activity mainly in international trade and agriculture, whilst social policy is where the regions and the State (which is also the main actor in foreign policy) are more active. Third, at least two levels of government (in some cases all of them) are significantly involved in the legislative activity in many sectors, even where the rationale for that is, at best, very questionable, indicating that they actually share a larger number of policy tasks than that suggested by the economic theory. It appears therefore that an excessive number of competences are actually shared among different levels of government. From an economic perspective, it may well be recommended that some competences be shared, but only when the balance between scale or spillover effects and heterogeneity of preferences suggests so. When, on the contrary, too many levels of government are involved in a certain policy area, the distinction between their different responsibilities easily becomes unnecessarily blurred. This may not only leads to a slower and inefficient policy-making process, but also risks to make it too complicate to understand for citizens, who, on the contrary, should be able to know who is really responsible for a certain policy when they vote in national,local or European elections or in referenda on national or European constitutional issues.

L'influenza del sonno sull'andamento temporale della consolidazione delle abilità procedurali

Background: It is well known, since the pioneristic observation by Jenkins and Dallenbach (Am J Psychol 1924;35:605-12), that a period of sleep provides a specific advantage for the consolidation of newly acquired informations. Recent research about the possible enhancing effect of sleep on memory consolidation has focused on procedural memory (part of non-declarative memory system, according to Squire’s taxonomy), as it appears the memory sub-system for which the available data are more consistent. The acquisition of a procedural skill follows a typical time course, consisting in a substantial practice-dependent learning followed by a slow, off-line improvement. Sleep seems to play a critical role in promoting the process of slow learning, by consolidating memory traces and making them more stable and resistant to interferences. If sleep is critical for the consolidation of a procedural skill, then an alteration of the organization of sleep should result in a less effective consolidation, and therefore in a reduced memory performance. Such alteration can be experimentally induced, as in a deprivation protocol, or it can be naturally observed in some sleep disorders as, for example, in narcolepsy. In this research, a group of narcoleptic patients, and a group of matched healthy controls, were tested in two different procedural abilities, in order to better define the size and time course of sleep contribution to memory consolidation. Experimental Procedure: A Texture Discrimination Task (Karni & Sagi, Nature 1993;365:250-2) and a Finger Tapping Task (Walker et al., Neuron 2002;35:205-11) were administered to two indipendent samples of drug-naive patients with first-diagnosed narcolepsy with cataplexy (International Classification of Sleep Disorder 2nd ed., 2005), and two samples of matched healthy controls. In the Texture Discrimination task, subjects (n=22) had to learn to recognize a complex visual array on the screen of a personal computer, while in the Finger Tapping task (n=14) they had to press a numeric sequence on a standard keyboard, as quickly and accurately as possible. Three subsequent experimental sessions were scheduled for each partecipant, namely a training session, a first retrieval session the next day, and a second retrieval session one week later. To test for possible circadian effects on learning, half of the subjects performed the training session at 11 a.m. and half at 17 p.m. Performance at training session was taken as a measure of the practice-dependent learning, while performance of subsequent sessions were taken as a measure of the consolidation level achieved respectively after one and seven nights of sleep. Between training and first retrieval session, all participants spent a night in a sleep laboratory and underwent a polygraphic recording. Results and Discussion: In both experimental tasks, while healthy controls improved their performance after one night of undisturbed sleep, narcoleptic patients showed a non statistically significant learning. Despite this, at the second retrieval session either healthy controls and narcoleptics improved their skills. Narcoleptics improved relatively more than controls between first and second retrieval session in the texture discrimination ability, while their performance remained largely lower in the motor (FTT) ability. Sleep parameters showed a grater fragmentation in the sleep of the pathological group, and a different distribution of Stage 1 and 2 NREM sleep in the two groups, being thus consistent with the hypothesis of a lower consolidation power of sleep in narcoleptic patients. Moreover, REM density of the first part of the night of healthy subjects showed a significant correlation with the amount of improvement achieved at the first retrieval session in TDT task, supporting the hypothesis that REM sleep plays an important role in the consolidation of visuo-perceptual skills. Taken together, these results speak in favor of a slower, rather than lower consolidation of procedural skills in narcoleptic patients. Finally, an explanation of the results, based on the possible role of sleep in contrasting the interference provided by task repetition is proposed.

The Efficiency of Microcredit Applied to Social Exclusion.

Microcredit has been a tool to alleviate poverty since long. This research is aimed to observe the efficiency of microcredit in the field of social exclusion. The development of questionnaires and use of existing tools was used to observe the tangible and intangible intertwining of microcredit and by doing so the effort was concentrated to observe whether microcredit has a direct effect on social exclusion or not. Bangladesh was chosen for the field study and 85 samples were taken for the analysis. It is a time period research and one year time was set to receive the sample and working on the statistical analysis. The tangible aspect was based on a World Bank questionnaire and the social capital questionnaire was developed through different well observed tools. The borrowers of Grameen Bank in Bangladesh, is the research sample whish shows a strong correlation between their tangible activity and social life. There are significant changes in tangible aspect and social participation observed from the research. Strong correlation between the two aspects was also found taking into account that the borrowers themselves have a vibrant social life in the village.

Expériences du sacré et (dé)figurations du Christ. Artaud, Beckett, Pasolini

« Dieu est mort » proclame à l’envi le fou nietzschéen. C’est sous l’égide inquiète de cette assertion paroxystique, traduisant ce «malaise de la culture» qu’évoquait Freud, que la pensée, la littérature et l’art du XXe siècle européen évoluent. Cependant, le christianisme dont ce cri signe l’extrême décadence, n’est pas seul à imprégner les productions artistiques de ce siècle, même les plus prétendument athées, mais avant tout la figure du Christ - autour de laquelle sont structurés tant cette religion que son système de croyance – semble, littéralement et paradoxalement, infester l’imaginaire du XXe siècle, sous des formes plus ou moins fantasmatiques. Ce travail se propose ainsi précisément d’étudier, dans une optique interdisciplinaire entre littérature, art et cinéma, cette dynamique controversée, ses causes, les processus qui la sous-tendent ainsi que ses effets, à partir des œuvres de trois auteurs : Artaud, Beckett et Pasolini. L’objectif est de fournir une clé de lecture de cette problématique qui mette en exergue comment « la conversion de la croyance », comme la définit Deleuze, à laquelle ces auteurs participent, n’engendre pas un rejet purement profanatoire du christianisme mais, à l’inverse, la mise en œuvre d’un mouvement aussi violent que libératoire qualifié par Nancy de « déconstruction du christianisme ». Ce travail entend donc étudier tout d’abord à la lumière de l’expérience intérieure de Bataille, l’imaginaire christique qui sous-tend leurs productions ; puis, d’en analyser les mouvements et les effets en les questionnant sur la base de cette dynamique ambivalente que Grossman nomme la « défiguration de la forme christique ». Les excès délirants d’Artaud, l’ironie tranchante de Beckett et la passion ambiguë de Pasolini s’avèrent ainsi participer à un mouvement commun qui, oscillant entre reprise et rejet, débouche sur une attitude tout aussi destructive que revitalisante des fondements du christianisme.

L'amministrazione Johnson e le origini della distensione. 1964-1968

La tesi analizza una parte della politica estera dell’amministrazione Johnson, e più specificamente l’avvio del dialogo con l’Urss in materia di non proliferazione e controllo degli armamenti e la revisione della China policy, inquadrando entrambe nell’adattamento della cold war strategy all’evoluzione sistema internazionale, argomentando che la distensione intesa come rilassamento delle tensioni e ricerca di terreno comune per il dialogo, fosse perlomeno uno degli strumenti politici che l’amministrazione scelse di usare. Il primo capitolo analizza i cambiamenti che interessarono il Blocco sovietico e il movimento comunista internazionale tra la fine degli anni Cinquanta e l’inizio degli anni Sessanta, soprattutto la rottura dell’alleanza sino-sovietica, e l’impatto che essi ebbero sul sistema bipolare su cui si basava la Guerra Fredda. Il capitolo secondo affronta più specificamente l’evoluzione delle relazioni tra Stati Uniti e Unione Sovietica, il perseguimento di una politica di distensione, dopo la crisi dei missili cubani, e in che relazione si trovasse ciò con lo status della leadership sovietica a seguito dei cambiamenti che avevano avuto luogo. Soffermandosi sulla questione del controllo degli armamenti e sul percorso che portò alla firma del Trattato di Non-proliferazione, si analizza come la nuova rotta intrapresa col dialogo sulle questioni strategiche sia stato anche un cambiamento di rotta in generale nella concezione della Guerra Fredda e l’introduzione della distensione come strumento politico. Il terzo capitolo affronta la questione della modifica della politica verso Pechino e il processo tortuoso e contorto attraverso cui l’amministrazione Johnson giunse a distaccarsi dalla China policy seguita sino ad allora.

Studio longitudinale sulle capacità cognitive del cane: discriminazione di quantità ed apprendimento per imitazione in relazione all'attaccamento

Il presente studio ha indagato e valutato alcune abilità cognitive del cane: la capacità di discriminare quantità e le capacità di apprendimento mediante imitazione; quest’ultima è poi stata messa in relazione con l’attaccamento nei confronti del proprietario. Per l’esecuzione della prima indagine sono stati messi appunto due test: il primo si è basato esclusivamente sulla presentazione di uno stimolo visivo: diversi quantitativi di cibo, differenti tra loro del 50%, sono stati presentati al cane; la scelta effettuata dai soggetti testati è stata premiata con differenti tipi di rinforzo differenziale o non differenziale. Il secondo test è stato diviso in due parti: sono stati presentati al cane diversi quantitativi di cibo sempre differenti tra loro del 50% ma nella prima parte del test l’input sensoriale per il cane è stato esclusivamente uditivo mentre nella seconda parte è stato sia uditivo che visivo. Ove è stato possibile è stato applicato ai cani un cardiofrequenzimetro al fine di eseguire una valutazione delle variazioni della frequenza cardiaca nel corso del test. Lo scopo è stato quello di valutare se i soggetti testati erano in grado di discriminare la quantità maggiore. La seconda indagine ha analizzato le capacità di apprendimento di 36 soggetti che sono stati suddivisi in cani da lavoro e pet. I soggetti protagonisti dello studio hanno eseguito il Mirror Test per la valutazione dell’apprendimento per imitazione. I soggetti presi in considerazione, sono stati sottoposti a scansione termografica all’inizio ed al termine del test ed è stata rilevata la loro frequenza respiratoria nella fase iniziale e finale del test. In 11 soggetti che hanno eseguito il precedente test è stato possibile eseguire anche il Strange Situation Test per la valutazione dell’attaccamento al proprietario; i test in questione sono stati videoregistrati ed analizzati per mezzo di un software preposto (OBSERVER XT 10).

The impact of intraclonal heterogeneity on the outcomes of Multiple Myeloma patients treated with new drugs

Understanding the biology of Multiple Myeloma (MM) is of primary importance in the struggle to achieve a cure for this yet incurable neoplasm. A better knowledge of the mechanism underlying the development of MM can guide us in the development of new treatment strategies. Studies both on solid and haematological tumours have shown that cancer comprises a collection of related but subtly different clones, a feature that has been termed “intra-clonal heterogeneity”. This intra-clonal heterogeneity is likely, from a “Darwinian” natural selection perspective, to be the essential substrate for cancer evolution, disease progression and relapse. In this context the critical mechanism for tumour progression is competition between individual clones (and cancer stem cells) for the same microenvironmental “niche”, combined with the process of adaptation and natural selection. The Darwinian behavioural characteristics of cancer stem cells are applicable to MM. The knowledge that intra-clonal heterogeneity is an important feature of tumours’ biology has changed our way to addressing cancer, now considered as a composite mixture of clones and not as a linear evolving disease. In this variable therapeutic landscape it is important for clinicians and researchers to consider the impact that evolutionary biology and intra-clonal heterogeneity have on the treatment of myeloma and the emergence of treatment resistance. It is clear that if we want to effectively cure myeloma it is of primarily importance to understand disease biology and evolution. Only by doing so will we be able to effectively use all of the new tools we have at our disposal to cure myeloma and to use treatment in the most effective way possible. The aim of the present research project was to investigate at different levels the presence of intra-clonal heterogeneity in MM patients, and to evaluate the impact of treatment on clonal evolution and on patients’ outcomes.