It is now widely accepted that the experience of pain is subject to cognitive influences that may determine the severity of subjectively perceived pain. Many of these top-down factors rely on memory-based processes, which in turn are related to prior experience, learned beliefs and behaviours about pain. As such, memory for pain heavily contributes to the physical pain experience. We posit that pain memory is bidirectional in that following each painful event a trace is stored and that these traces in turn may modify future pain perception prospectively. The following body of work explores aspects of what we have termed a memory template for pain. The results of these chapters taken together, examine these bidirectional aspects of short-term memory for pain employing a recall pain task. Specifically, we explore how, after an acute pain event, a short-term mental representation of the initial event persists. We show that during this time, sensory re-experiencing of the painful event is possible. Furthermore, we investigate aspects of recalled pain, namely intensity and vividness. Data suggests that the intensity and the vividness of this mental representation are determined by the intensity of the initial stimulus, as well as the time-to-test delay. We identify regions that characterise short-term memory for pain. Following on from studies in motor and visual imagery, we explore how pain imagery in the form of recall may affect subsequent pain perception. Our results demonstrate that the inclusion of pain-related imagery preceding physical pain events reduces affective qualities of pain. Testing healthy, naïve subjects, we replicate the effect observed in studies using attention management and imagery strategies, which normally require extensive training. Finally, in a cohort of neuropathic pain patients we show significant reductions in white matter connectivity between areas responsible for working and prospective memory. Collectively, these studies emphasise and elucidate the role of short-term memory of pain in physical pain perception. Acting both retrospectively and prospectively, cognitive reinforcement can increase or decrease the subjective feeling of pain, and therefore manipulating how pain is recalled may have therapeutic potential.

Humans have an innate ability to deal with numerosity and other aspects of magnitude. This ability is generally honed through education in and experience with mathematics, which necessarily changes the brain structurally and functionally. These changes can be further manipulated through non-invasive electrical brain stimulation. Studying these processes in the case of maths not only constitutes research of great practical impact – given the importance of numerical skills in today's society – but also makes use of maths as a suitable domain in which to study plasticity. In this thesis, I aimed to explore how expertise with numbers shapes brain and behaviour, and also the degree to which processing numbers is similar to other domains in terms of the necessity of healthy brain regions believed to underlie normal processing within and across these domains. In Study 1, behavioural and structural brain differences were found cross-sectionally between mathematicians and non-mathematicians. A double dissociation between those groups was found between grey matter density in the frontal lobe and behavioural performance: their correlation was positive for mathematicians but negative for controls. These effects may have been caused by years of experience, by congenital predispositions, or, plausibly, by both of these factors, whose disambiguation is non-trivial. Study 2 used transcranial random noise stimulation (tRNS) to assist arithmetic learning. A novel montage was used to enhance brain function during the stage when it is believed to be most involved. Real as compared to sham tRNS enhanced reaction times (RTs) and learning rate on a calculation-based task, but not on a retrieval-based task. The effects were only observed in conditions of high task difficulty. Study 3 examined structural MRI measures before and after arithmetic training to determine how either frontal or parietal tRNS applied with the task changes the structure of the brain longitudinally as compared to sham. Previous results (including those of Study 2) of behavioural facilitation in terms of enhanced RTs to calculation problems were replicated, and further interpreted. Both frontal and parietal tRNS modulated the changes that occurred, pre-to-post training, in terms of cortical volume and gyrification of frontal, parietal and temporal areas. Study 4 investigated the shared neural and cognitive resources used for processing numerical magnitude and musical pitch, by probing how stimulus-response compatibility (SRC) effects for each of the two dimensions compare in a group of mainly temporoparietal lesion patients with numerical impairments versus controls. A double dissociation was found in that numerically impaired patients did not show the number-based SRC effect but did show the pitch-based one, while control subjects demonstrated the opposite trend. Overall, the results of these studies leave us with three main messages. First, expertise in numbers and mathematics, whether acquired through years of experience (Study 1) or through a few days of tRNS-assisted training (Study 3), appears to be associated with complex changes in the morphology of several brain structures. Some – but not all – of these structures are maths-relevant, and, in the case of tRNS-assisted training, they are distal to the site of the stimulating electrodes. Second, tRNS can improve performance in arithmetic (Studies 2 and 3), although the mechanisms by which this occurs are not yet fully understood, neither neurally nor behaviourally. Third, I found (Study 4) that brain lesions leading to impairment in the number domain do not necessarily affect processing in other domains – such as pitch – that are otherwise linked to number via a putative common code in the parietal lobes.

Behaviour is guided by accumulated experience, valuation and comparison. While many aspects associated with these functions are mediated by the frontal lobes, the precise contribution from particular regions remains debated. This thesis will deal with how an organism comes to select an option and will specifically focus on the role of the orbitofrontal cortex (OFC) in two mechanisms in this process: learning of outcome specificities and selecting between multiple options based on their expected values. Despite evidence emphasizing anatomical and connective heterogeneity within this structure, the OFC is often regarded as a uniform region. This thesis aims to resolve some of this uncertainty by assuming that the medial and lateral regions of the OFC contribute differentially to learning and decision-making. Two distinct methodologies were used in these investigations. First, the contribution of the medial OFC to social and emotional processing was examined. The findings from this study disprove previously held beliefs that the medial regions of the OFC guide social and emotional behaviours, but indicted a role for this region in value-guided decision-making. The second study examined functional differences between the lateral and medial OFC by making circumscribed lesions to either region in macaque monkeys. The animals performed a number of 3-armed bandit tasks which were designed to investigate different aspects of value assignment and comparison. The results show that while lateral OFC was required for "credit assignment" – the correct assignment of values to visual cues – medial OFC was critical for comparison of the cues' values during decision-making. In unchanging probabilistic environments, mOFC lesions induced decision-making impairments when value comparison was difficult without affecting credit assignment and associative learning. By contrast, lateral OFC lesions caused the opposite pattern of impairment. The final study used human-neuroimaging techniques to investigate the differential representation of outcome-specific contingency learning and found not only that the expectation of a unique outcome facilitated learning and memory recall but that this was supported by a neural network which included the lateral regions of the OFC and the anterior cingulate cortex. Activity in the mOFC did not correlate with outcome-specific contingency learning but instead reflected both the value associated with the receipt and expectation of a reward. Taken together, the results from this thesis suggest that specific parts of the OFC make markedly different contributions to these very different cognitive functions.

Stress and anxiety negatively impact the working memory system by competing for executive resources. Broad memory deficits have been reported in individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS). We investigated anxiety and physiological stress reactivity in relation to visuospatial working memory impairments in 20 children with 22q11.2DS and 32 typically developing children (M = 11.10 years, SD = 2.95). Results indicate reduced post-stress RSA recovery and overall increased levels of cortisol in children with 22q11.2DS. Additionally, anxiety mediated the relationship between 22q11.2DS and visuospatial working memory impairment. However, there was no indication that stress response physiology mediated this association. Results suggest that anxiety exacerbates impaired working memory in children with 22q11.2DS. Thus, treatment and intervention methods for children with 22q11.2DS should address anxiety related symptomology.

No description available.

Le contrôle exécutif de l'action fait référence a la capacité de l'homme a contrôler et adapter son comportement de manière flexible, en lien avec ses états mentaux internes. Il repose sur l’évaluation des conséquences des actions pour ajuster les choix futurs. Les actions peuvent être renforcées ou dévalues en fonction de la valeur affective des conséquences, impliquant notamment les ganglions de la base et le cortex préfrontal médian. En outre, les conséquences des actions portent une information, qui permet d'ajuster le comportement en relation avec des croyances internes, impliquant le cortex préfrontal. Ainsi, les conséquences des actions portent deux types de signaux : (1) Une valeur affective, qui représente l’évaluation de la conséquence de l'action selon les préférences subjectives, issue de l'apprentissage par renforcement ; (2) Une valeur de croyance, mesurant comment les actions correspondent aux contingences externes, en lien avec l’inférence bayésienne. Cependant, la contribution de ces deux signaux a la prise de décision reste méconnue. Dans cette these, nous avons étudie la pertinence de cette dissociation aux niveaux comportemental et cérébral. Nous présentons plusieurs expériences comportementales permettant de dissocier ces deux signaux de valeur, sous la forme de taches d'apprentissage probabiliste avec des structures de récompense stochastiques et changeantes. Nous avons construit un modelé établissant les fondations fonctionnelles et computationnelles de la dissociation. Il combine deux systèmes en parallèle : un système d'apprentissage par renforcement modulant les valeurs affectives, et un système d’inférence bayésienne modulant les croyances. Le modèle explique mieux le comportement que de nombreux modèles alternatifs. Nous avons ensuite étudie, en IRM fonctionnelle, si les représentations dépendantes et indépendantes du choix des croyances et des valeurs affectives avaient des bases neurales distinctes. L’activité du cortex préfrontal ventromédian (VMPFC) et du cortex mid-cingulaire (MCC) corrélé avec les deux variables dépendantes du choix. Cependant, une double-dissociation a été identifiée concernant les représentations indépendantes du choix, le VMPFC étant spécifique des croyances alors que le MCC est spécifique des valeurs affectives. En outre, l’activité du cortex préfrontal latéral augmente lorsque les deux valeurs de décision sont proches et que le choix devient difficile. Ces résultats suggèrent qu'avant la décision, le cortex préfrontal ventromédian (VMPFC) et le cortex mid-cingulaire (MCC) encodent séparément les croyances et les valeurs affectives respectivement. Le cortex préfrontal latéral (LPFC) combine les deux signaux pour prendre une décision, puis renvoie l'information du choix aux régions médianes, probablement pour actualiser les deux signaux de valeur en fonction des conséquences du choix. Ces résultats contribuent a élucider les mécanismes cérébraux de la prise de décision dans le cortex préfrontal. / Executive control relates to the human ability to monitor and flexibly adapt behavior in relation to internal mental states. Specifically, executive control relies on evaluating action outcomes for adjusting subsequent action. Actions can be reinforced or devaluated given affective value of outcomes, notably in basal ganglia and medial prefrontal cortex. Additionally, outcomes convey information to adapt behavior in relation to internal beliefs, involving prefrontal cortex. Accordingly, action outcomes convey two major types of value signals: (1) Affective values, representing the valuation of action outcomes given subjective preferences and stemming from reinforcement learning; (2) Belief values about how actions map onto outcome contingencies and relating to Bayesian inference. However, how these two signals contribute to decision remains unclear, and previous experimental paradigms confounded them. In this PhD thesis, we investigated whether their dissociation is behaviorally and neurally relevant. We present several behavioral experiments dissociating these two signals, in the form of probabilistic reversal-learning tasks involving stochastic and changing reward structures. We built a model establishing the functional and computational foundations of such dissociation. It combined two parallel systems: reinforcement learning, modulating affective values, and Bayesian inference, monitoring beliefs. The model accounted for behavior better than many other alternative models. We then investigated whether beliefs and affective values have distinct neural bases using fMRI. BOLD signal was regressed against choice-dependent and choice-independent beliefs and affective values. Ventromedial prefrontal cortex (VMPFC) and midcingulate cortex (MCC) activity correlated with both choice-dependent variables. However, we found a double-dissociation regarding choice-independent variables, with VMPFC encoding choice-independent beliefs, whereas MCC encoded choice-independent affective values. Additionally, activity in lateral prefrontal cortex (LPFC) increased when decision values (i.e. mixture of beliefs and affective values) got closer to each other and action selection became more difficult. These results suggest that before decision, VMPFC and MCC separately encode beliefs and affective values respectively. LPFC combines both signals to decide, then feeds back choice information to these medial regions, presumably for updating these value signals according to action outcomes. These results provide new insight into the neural mechanisms of decision-making in prefrontal cortex.

A síndrome de Kallmann (SK) é um distúrbio raro, caracterizado pela presença do Hipogonadismo Hipogonadotrófico Idiopático (HHI) associado à anosmia ou hiposmia (ausência ou déficit no sentido do olfato, respectivamente). O HHI tem como principal causa a deficiência do hormônio liberador de gonadotrofina (GnRH), com heterogeneidade genética significativa. Clinicamente é caracterizada por níveis plasmáticos baixos dos hormônios luteinizante (LH) e folículo-estimulante (FSH) associados com baixas concentrações de esteroides sexuais. O estabelecimento de um fenótipo cognitivo claro da SK pode ajudar na compreensão sobre o desenvolvimento das funções cognitivas humanas e a informar para um melhor manejo do paciente, com um acompanhamento mais apropriado. Neste estudo foi realizada uma bateria de avaliação neuropsicológica, caracterizando aspectos referentes aos quocientes intelectuais, atenção, funções executivas, memória, linguagem e habilidades visuoespaciais. Como resultados, o grupo de participantes diagnosticado de SK apresentou desempenho inferior em todas as áreas avaliadas, quando comparado ao grupo controle. Todavia, seu desempenho de maneira geral esteve dentro das faixas média e média-inferior, caracterizando assim um déficit leve das funções neuropsicológicas avaliadas. A memória declarativa de longa duração, no entanto, no grupo clínico esteve bastante prejudicada, com classificação dentro do espectro deficitário. Este resultado, aliado ao desempenho inferior em atividades que exigiam um julgamento de origem temporal e ao comprometimento da aprendizagem de associações condicionais arbitrárias (entre estímulos e respostas), sugere que a maior característica cognitiva presente no grupo clínico está na dificuldade de reter e selecionar informações apropriadas dentre os diversos estímulos e não apenas na recuperação destas informações. / The Kallmann syndrome (KS) is a rare disorder characterized by the presence of hypogonadotropic hypogonadism Idiopathic (IHH) associated with anosmia or hyposmia (absence or deficit in the sense of smell, respectively). The HHI\'s main causes deficiency of gonadotropin-releasing hormone (GnRH), with significant genetic heterogeneity. Clinically, it is characterized by low plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) associated with low concentrations of sex steroids. The establishment of a clear cognitive phenotype of SK can help in understanding the development of human cognitive functions and to report to a better management of the patient with a more appropriate accompaniment. In this study a battery of neuropsychological evaluation was performed, featuring aspects of intellectual quotients, attention, executive functions, memory, language and visuospatial skills. As a result, the diagnosed group of participants of KS showed lower performance in all areas evaluated, when compared to the control group. However, its performance in general was in the middle and lower-middle ranges, characterizing a slight deficit of assessed neuropsychological functions. The declarative memory of long term, however, in the clinical group was significantly impaired classified within the spectrum deficit. This result, coupled with lower performance in activities requiring a judgment of temporal origin and impairment of learning arbitrary conditional associations (between stimuli and responses), suggests that higher cognitive feature present in the clinical group is the difficulty of retaining and select information appropriate from the various stimuli, not just the recovery of this information.

Cette thèse décrit l'intégration multimodale voix-visage pour la perception du genre à l'aide de méthodes comportementales et d'imagerie cérébrale. Dans une première étude psychophysique, les observateurs ont départagé des paires de stimuli voix-visage selon le genre du visage, de la voix ou du stimulus (sans instruction particulière). Une seconde étude a reproduit ce paradigme en ajoutant du bruit visuel et/ou auditif. Conformément à nos résultats théoriques, tâche et bruit peuvent tous deux être modélisés comme des facteurs de pondération. Les deux effets pourraient refléter des changements similaires de hiérarchie fonctionnelle avec la communication par cohérence comme implémentation potentielle de ce mécanisme en termes de modulation sélective de l'information par synchronisation des rythmes d'oscillation neuronaux. Une asymétrie en faveur de la modalité auditive a été trouvée dans les deux études comportementales ainsi que deux interactions : un effet multiplicatif du genre significatif lorsqu'on juge le visage et le stimulus ; un effet de cohérence significatif lorsqu'on juge le visage ou la voix. Une troisième étude en IRMf s'est intéressée aux modulations de connectivité effective entre l'aire fusiforme du visage et l'aire temporale de la voix durant la présentation de stimuli voix-visage en prêtant attention au genre du visage, de la voix ou du stimulus. Une telle modulation a été trouvée dans les tâches du visage et du stimulus en réponse au genre, et dans les tâches du visage et du stimulus en réponse à l'incohérence, deux modulations indépendantes qui pourraient être supportées par l’architecture anatomique en double contre-courant / This thesis describes face-voice multimodal gender integration using complementary behavioral and brain imaging techniques. In a first psychophysical study, observers judged pairs of face-voice stimuli according to face, voice or stimulus (no specific instruction given) gender. A second study tested the bottom-up effect of adding visual and/or auditory noise in the same paradigm. Top-down task and bottom-up noise could both be modeled as weighting effects, as predicted by our theoretical results. Both effects might reflect similar shifts in functional hierarchy. Communication through coherence offers a potential explanation for the neural basis of such a mechanism in terms of selective modulation of segregated cortical streams by oscillatory rhythm synchronization. An asymmetry in favor of the auditory modality was found in both behavioral experiments as well as two interaction effects, first a multiplicative gender effect in the face and stimulus tasks, second an effect of gender coherence in the face and voice tasks. In a third experiment we used fMRI to investigate effective connectivity modulations between the Fusiform Face Area and Temporal Voice Area during the presentation of face-voice stimuli while attending to either face, voice or any gender information. We found a change in effective connectivity for stimulus and face tasks in response to gender information, and for face and voice tasks in response to gender incoherence. These two independent modulations could be supported by the anatomical dual counterstream architecture

L’innovation thérapeutique est limitée en psychiatrie. De nombreux médicaments sélectionnés sur la base de résultats encourageants dans les essais chez l’animal se révèlent décevants lors des essais cliniques. La validité limitée des modèles animaux, et leur utilisation pour tenter de mimer des pathologies définies de façon catégorielle sur la base de regroupement de symptômes de surface sans lien clair avec les processus cérébraux, les mécanismes biologiques ou la génétique, participent à ces difficultés. Une branche des neurosciences cognitives, l’étude de l’apprentissage par renforcement, associée à l’utilisation d’interventions pharmacologiques ciblées chez le sujet malade ou le sujet sain, représente une opportunité de mieux caractériser les processus cérébraux sous-tendant certaines dimensions cardinales des pathologies psychiatriques. Nous illustrons l’utilisation de l’étude de l’apprentissage par renforcement avec intervention pharmacologique dans deux études expérimentales. La première cherche à caractériser l’effet de l’aripiprazole, un antipsychotique atypique, chez des patients atteints du syndrome Gilles de la Tourette, en utilisant une tâche d’apprentissage contrefactuel, évaluant la capacité à apprendre non seulement des conséquences de ses actions, mais également des conséquences hypothétiques d’actions alternatives possibles. La seconde étude, randomisée contrôlée et en double aveugle, étudie l’effet de deux classes différentes d’antidépresseurs, l’escitalopram et l’agomélatine, chez le sujet sain. L’effet de leur administration est évalué à court terme (3 jours) et à long terme (8 semaines) dans deux tâches probabilistes de sélection de stimulus, l’une simple, l’autre avec renversements occasionnels. L’utilisation de cette approche pourrait participer à la définition d’endophénotypes et, en collaboration avec la recherche préclinique, aider à la création de nouveaux modèles animaux pour en améliorer la valeur prédictive. / Successful new drug development has declined in psychiatry in the last decades. This is in part the resut of a high failure rate in translating positive preclinical efficacy results to positive clinical trials. Limitations in the validity of animal models and shortcomings in the usefullnes of the current categorical diagnostic system. Cognitive neurosciences and particularly reinforcement learning and its computational analysis might provide biomarkers required to develop new ways of classifying mental disorders on the basis of both observable behaviour and neurobiological measues. Used in conjunction with pharmacological challenges, it may bring new insights into the physiopahtology and brain mechanisms underlying psychiatric disorders. It may also help design new animal models with imporved predictive validity for the develoment of medications relying on innovative mechanisms of action. We illustrate the use of reinforcement learning and pharmacological challenge in two experimental studies. In the first experiment, we administered a reinforcement learning task that involves both direct learning from obtained outcomes and indirect learning from forgone outcomes to two groups of Gilles de la Tourette patients, one receiving aripiprazole, one unmedicated and to a group of healty subjects. In the second experiment, we administered two probabilistic stimulus selection learning tasks (one simple, one with occasional reversals) to healthy subjects randomly and blindly allocated to either escitalopram, a typical serotonin reuptake inhibitor, agomelatine, an antidepressant with a different mechanism of action, or placebo. The experiment compard the effect of these two classes of antidepressants to placebo after both short term (3 days) and long term (8 weeks) treatment. These experiments bring insights into the understanding of the clinical condition studied, and the effects of the drugs tested. Implications of this approach for the translational approach to drug development is discussed.

A self-adaptive software is developed to predict the stock market. It’s Stock Prediction Engine functions autonomously when its skill-set suffices to achieve its goal, and it includes human-in-the-loop when it recognizes conditions benefiting from more complex, expert human intervention. Key to the system is a module that decides of human participation. It works by monitoring three mental states unobtrusively and in real time with Electroencephalography (EEG). The mental states are drawn from the Opportunity-Willingness-Capability (OWC) model. This research demonstrates that the three mental states are predictive of whether the Human Computer Interaction System functions better autonomously (human with low scores on opportunity and/or willingness, capability) or with the human-in-the-loop, with willingness carrying the largest predictive power. This transdisciplinary software engineering research exemplifies the next step of self-adaptive systems in which human and computer benefit from optimized autonomous and cooperative interactions, and in which neural inputs allow for unobtrusive pre-interactions. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection