Bildgebende Studien haben gezeigt, dass bei schizophrenen Patienten Positivsymptome mit Veränderungen mesolimbischer Aktivierungsmuster unter Einbeziehung des Nucleus accumbens in Zusammenhang stehen. Hierbei ist von besonderem Interesse, dass der Nucleus accumbens Teil des Belohnungssystems ist, wobei die integrale „Bewertung“ belohnungsanzeigender Reize präfrontalen kortikalen Strukturen, insbesondere dem anterioren Zingulum, zuzurechnen ist. Bereits in der Antizipationsphase potentiell belohnender Reize, werden vermutlich zur Berechnung von Prädiktionsabweichungen dopaminerge Signale in der VTA generiert und modulieren den Nucleus accumbens. Es gibt zahlreiche Hinweise, dass glutamaterge Neurone des anterioren Zingulums die Dopaminausschüttung im Nucleus accumbens beeinflussen, und dass diese Modulation bei Erkrankungen wie der Schizophrenie beeinträchtigt ist. Ziel der vorliegenden Arbeit war es, mittels funktioneller Magnetresonanztomographie und Protonen Magnetresonanzspektroskopie, Hinweise über den Zusammenhang zwischen der glutamatergen Neurotransmission des ACC und belohnungsassoziierter Dopaminausschüttung im Nucleus accumbens bei 23 gesunden Probanden und bei 23 unmedizierten schizophrenen Patienten zu erlangen. Die Ergebnisse weisen darauf hin, dass die gegenseitige Modulation von anteriorem Zingulum und Nucleus accumbens bei schizophrenen Patienten gestört ist. Dieses und weitere Ergebnisse wurden im theoretischen Rahmen der NMDA-Rezeptor-Hypoaktivität und einer gestörten Balance zwischen Dopamin-D1- und Dopamin-D2-Rezeptor-Aktivität als pathophysiologische Korrelate schizophrener Erkrankungen diskutiert. / Imaging studies have demonstrated that for schizophrenic patients a correlation exists between positive symptoms and changes in the patterns of mesolimbic activity. Especially the changes in the ncl. accumbens (Nac) were interpreted in connection with the reward system. The signals indicating reward are thought to be processed by the anterior cingulum (ACC). These structures attribute meaning to the reward signals. In the anticipation phase of a potentially rewarding stimulus, dopaminergic signals from the VTA are generated in prediction of expected or aberrant outcome, thus modulating the Nac. Data indicate a direct modulation of the Nac. by glutamatergic neurons of the anterior cingulum. A major aim of this thesis is to establish a connection between the reward associated dopaminergic signals of the ncl. accumbens and the glutamatergic projections of the acc in unmedicated schizophrenic patients and healthy controls. The methods included measurements of proton magnetic resonance spectroscopy (1H-MRS) and functional MRI-scans done at a 3-Tesla tomograph. The paradigm applied was a modified version of the monetary incentive delay paradigm (Knutson et al. 2000). In healthy volunteers we found a significant negative correlation between the glutamate concentration in the ACC and the BOLD-contrast in the Nac (reward versus neutral), in contrast to the findings in schizophrenic patients. A significant higher BOLD-contrast was seen in the anticipation phase in healthy controls. The results were incorporated in a model of NMDA-R-Hypoaktivity. In addition to discussing the functional aspects for the structures involved the model was further expanded to include the hypothesis of a disturbed balance between dopamine-D1- and -D2-receptor activity and a dysfunctional hippocampal gating-process. The so constructed model suggests a profound striato-thalamo-cortical filter disturbance as the basis of the observed aberrations in the reward processing in schizophrenic disorders.

Ausgangspunkt dieser Dissertation ist, dass mit stabilen Präferenzen unvereinbares Verhalten für die Standardökonomik eine Herausforderung darstellt. Eines der sich stellenden Probleme ist, dass sich wandelnde Präferenzen der normativen Analyse abträglich sind: Wenn nicht vorhersagbar ist, ob und wie Präferenzen abhängig von der Situation und von institutionellen Arrangements variieren, lässt sich keine optimale Wirtschaftspolitik bestimmen. Es wird argumentiert, dass die Ökonomik daher auch in Betracht ziehen muss, wie Präferenzen evolvieren und wie ökonomische Akteure Informationen - z. B. Wahrscheinlichkeiten und Auszahlungen -verarbeiten. In den folgenden Kapiteln werden zwei Studien vorgestellt, die dieses Ziel verfolgen, indem sie den Prozess der Entscheidungsfindung experimentell untersuchen. Die erste Studie, "Kognitive Last erhöht Risikoaversion", zeigt, dass eine spezifische Änderung des Entscheidungsumfelds - nämlich eine Erhöhung der kognitiven Last - einen messbaren Einfluss auf die Risikoeinstellungen der Versuchspersonen hatte. Zudem werden die beobachteten Verhaltensänderungen in Verbindung zu existierenden Mehr-System-Modellen der Entscheidungsfindung gesetzt. Die ebenfalls gemessenen Reaktionszeiten bestätigt die Interpretation, dass die Entscheidungsfindung unter Risiko das Produkt interagierender Systeme im menschlichen Hirn ist. Die zweite Studie, "Soziales Lernen auf Finanzmärkten", verfolgt das Ziel, die normalerweise verborgenen Komponenten Präferenzen und Überzeugungen beobachtbar zu machen. Zu diesem Zweck absolvierten Versuchspersonen ein Experiment, während ihre Hirnaktivierung per funktioneller Magnetresonanztomografie gemessen wurde. Dies erweitert den analysierbaren Datensatz über die getroffenen Entscheidungen hinaus um Maße der Hirnaktivierung. Dadurch trägt diese Studie zur Identifizierung der Faktoren bei, die bestimmen, in welchem Umfang wir aus der Beobachtung der Entscheidungen anderer lernen. / The point of departure of this dissertation is that behavior which is inconsistent with stable preferences poses a challenge for mainstream economics. One of the issues that arise is that changing preferences are detrimental to the objective of normative economics: If one cannot predict whether and how people’s preferences vary across situations or institutions, one cannot determine which economic policy would be optimal. Based on this, it is argued that economics has to take into account how preferences evolve and how information - e.g., probabilities and payoffs - is processed by economic agents. In the following two chapters, two experimental studies are presented that pursue this goal by investigating the process by which people make decisions. The first study, "Cognitive load increases risk aversion," shows that a specific change in the environment - in this case, an increase in cognitive load - had a measurable impact on subjects’ risk attitudes. Importantly, it also relates the observed changes to existing dual-system models of decision making. The response times which were recorded in addition to subjects’ choices contribute to the interpretation of the study’s findings, since they support the view that decision making under risk is the product of interacting systems in the human brain. The second study, "Social learning in asset markets," has the objective of making the latent components preferences and beliefs observable. To this end, subjects participated in a social-learning experiment while their brain activation was recorded via functional magnetic-resonance imaging. This enlarges the analyzable dataset through measures of subjects’ brain activation in addition to subjects’ choices. In doing so, the study contributes to identifying the factors that shape to what extent we learn from observing the choices of other human beings.

Muitas operações cognitivas requerem velocidade de processamento de informação (VPI) suficiente para serem executadas dentro do prazo permitido, sendo que VPI retardada geralmente está subjacente a déficits atencionais. A desaceleração no tempo de resposta é particularmente evidente em pacientes com traumatismo crânio-encefálico, doença de Parkinson, depressão, demência e esclerose múltipla (EM). A importância de compreender os déficits de VPI e o desenvolvimento de programas efetivos de reabilitação é, portanto, crítico. Devido à sua alta validade preditiva e à sua fácil administração, o Symbol Digit Modalities Test (SDMT) é um dos testes clínicos mais amplamente utilizados para a avaliação cognitiva de pacientes com menor VPI. No entanto, além de avaliar a presença e gravidade de seus déficits, é interessante determinar as regiões cerebrais responsáveis por essa função e sua integração. Devido à sua não invasividade e ao seu bom nível de confiabilidade, a técnica de Imagem de Ressonância Magnética Funcional Dependente do Nível de Oxigenação no Sangue (BOLD-fMRI) é a ferramenta mais apropriada para esse fim. Logo, o objetivo do presente estudo foi o mapeamento funcional cerebral de VPI durante o desempenho de uma tarefa (SDMT) adaptada para o ambiente da ressonância em um grupo de voluntários saudáveis jovens. 16 controles saudáveis destros foram recrutados e submetidos à avaliação cognitiva com a versão oral do SDMT antes da aquisição de imagens. IRM foi adquirida em um sistema de 3T (Philips Achieva). Imagens funcionais (BOLD) foram adquiridas com uma sequência EPI. O experimento consistiu de seis blocos de 30 s de controle intercalados com cinco blocos de 30 segundos de tarefa (SDMT). Durante os blocos de tarefa, um símbolo foi apresentado a cada 2 segundos e ao participante foi requerido que associasse o número correspondente ao símbolo apresentado baseando-se em uma chave de resposta. Durante os blocos de controle, um número foi apresentado a cada 2 segundos e ao participante foi requerido que lesse silenciosamente o número em questão. Mapas paramétricos estatísticos foram obtidos para estudo de localização funcional utilizando o Modelo Linear Geral com um regressor boxcar convoluído com uma função de resposta hemodinâmica canônica (p-FDR < 0,01). Foi realizada a correlação bivariada entre as séries temporais médias das regiões associadas à tarefa para estudo de integração funcional (p-FDR < 0.0001). As informações de localização e integração funcionais foram inseridas em analise de conectividade efetiva. Ativações foram observadas na rede frontoparietal e no córtex occipital para análises individual e em grupo. Análise de conectividade efetiva para a arquitetura do sistema revelou o declive em posição serial com o giro lingual, o cúneo e duas regiões paralelas (pré-cúneo e lóbulo parietal superior), a partir do qual a informação converge para o giro frontal inferior e se bifurca para os giros frontais médios esquerdo e direito. Um modelo de rede envolvendo áreas relacionadas à VPI foi obtido e pode servir como referência para investigações futuras deste processo cognitivo em grupos clínicos, combinadas com estudos de neuroplasticidade cerebral. / Many cognitive operations require sufficient information processing speed (IPS) to be executed within the allowed time frame, with delayed IPS often underlining attentional deficits. The deceleration in response time is particularly evident in patients with traumatic brain injury, Parkinson\'s disease, depression, dementia and multiple sclerosis (MS). The importance of understanding IPS deficits and developing effective rehabilitation programs is therefore critical. Because of its high predictive validity and easy administration, the Symbol Digit Modalities Test (SDMT) is one of the most widely used clinical tests for the cognitive assessment of patients with lower IPS. However, in addition to evaluating the presence and severity of its deficits, it is interesting to determine the brain regions responsible for this function and its integration. Because of its non-invasiveness and its good level of reliability, the BOLD-fMRI technique is the most appropriate tool for this purpose. Therefore, the aim of the present study was the functional brain function mapping of IPS during the performance of a task (SDMT) adapted to the resonance environment in a group of healthy young volunteers. 16 healthy right controls were recruited and submitted to cognitive assessment with the oral version of SDMT prior to image acquisition. MRI was acquired in a 3T system (Philips Achieva). Functional images (BOLD) were acquired with an EPI sequence. The experiment consisted of six blocks of 30 s of control intercalated with five blocks of 30 seconds of task (SDMT). During the task blocks, a symbol was displayed every 2 seconds and the participant was required to associate the number corresponding to the displayed symbol based on a response key. During the control blocks, a number was displayed every 2 seconds and the participant was required to silently read the number in question. Statistical parametric maps were obtained for functional localization study using the General Linear Model with a boxcar regressor convolved with a canonical hemodynamic response function (p-FDR <0.01). The bivariate correlation between the mean time series of the regions associated with the task for functional integration study (p-FDR <0.0001) was performed. The functional location and integration information was inserted into effective connectivity analysis. Activations were observed in the frontoparietal network and in the occipital cortex for individual and group analyzes. Effective connectivity analysis for the system architecture revealed the declive in serial position with the lingual gyrus, the cuneus and two parallel regions (precuneus and superior parietal lobule), from which the information converges to the inferior frontal gyrus and bifurcates to the left and right middle turns. A network model involving areas related to IPS has been obtained and may serve as a reference for future investigations of this cognitive process in clinical groups, combined with studies of cerebral neuroplasticity.

Orientador: Prof. Dr. João Ricardo Sato / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Engenharia da Informação, 2014. / O transtorno do déficit de atenção e hiperatividade (TDAH) é um transtorno de neurodesenvolvimento, associado a fatores genéticos e ambientais, compreendendo a sintomatologia: desatenção, hiperatividade e impulsividade. Neste estudo, utilizou-se a teoria dos grafos e a ressonância magnética funcional (fMRI) para obtenção de um método de distinção entre pacientes e controles para o suporte ao diagnóstico do TDAH. O objetivo deste trabalho foi a comparação das medidas de conectividade cerebral de pacientes (TDAH) com sujeitos controle (desenvolvimento típico) por meio da fMRI, medidas de centralidade e o Support Vector Machine (SVM). Utilizou-se a base de dados ADHD-200. Construiu-se um classificador a partir das características extraídas das redes de conectividade cerebral na tentativa de se distinguir entre sujeitos controle e pacientes. O método envolveu o uso do SVM em características de imagens de fMRI, em dois pares de grupos: controle vs pacientes (TDAH) e TDAH subtipos. Foram modelados grafos ponderados e não ponderados e calculadas algumas medidas de centralidade. Na análise por site dos sujeitos controle versus TDAH desatento foram observadas diferenças na conectividade das regiões cerebrais intermediárias, com escore de 63% no limiar 0,25 da centralidade betweenness no site 4. Com grafo ponderado, outras diferenças de conectividade cerebral foram observadas, com escore de 73% para a medida betweenness entre as regiões cerebrais no site 6. A análise dos portadores de TDAH subgrupo desatento versus combinado, no site 6 foram observadas distinções na medida betweenness e no degree das conexões das regiões cerebrais, no limiar de 0,15, com escores de 73% e 77% respectivamente. Em face aos resultados apresentados é possível encontrar algumas distinções nas conexões cerebrais, principalmente entre os sujeitos portadores de TDAH desatento versus TDAH combinado, a partir da extração das características cerebrais, com utilização de algumas medidas de centralidade como variáveis preditoras para o algoritmo SVM. / The Attention Deficit and Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder associated with genetic and environmental factors, including the symptoms: inattention, hyperactivity and impulsivity. In this study, we used graph theory and functional magnetic resonance imaging (fMRI) to obtain a method for distinguishing between patients and controls to support the diagnosis of ADHD. The aim of this study was to compare measures of brain connectivity between patients (ADHD) and control subjects (typically developing). We used through fMRI, measures of centrality, support vector machines (SVM) and the database ADHD-200. We built a classifier based on the features extracted from the brain connectivity networks in an attempt to distinguish between patients and control subjects. The method involved the use of SVM in connectivity features in two sets of groups: Control vs. patients (ADHD) and inattentive ADHD vs Combined. Measures of weighted and unweighted graphs were modeled and some measures of centrality were extracted. In the unweighted graph analysis by site and inattentive ADHD vs control subjects comparison, differences were found in the connectivity pattern, with a score of 63% for betweenness centrality in site 4. In weighted graph, further differences in brain connectivity were observed, with a score of 73% also in betweenness in site 6. In this same site, the analysis of patients with ADHD inattentive versus combined subgroup, achieved scores of of 73% (betwenness) and 77% (degree) in unweighted graph analysis. In conclusion, we found some differences in brain connectivity patterns, especially between subjects with ADHD inattentive versus combined ADHD. By using some measures of centrality as predictors for the SVM algorithm, we found moderate classification accuracy in individual groups¿ prediction.

In this dissertation the effects of variations in stimulus properties and CTOA, in auditory attention tasks were explored using recently developed approaches to EEG analysis including LIMO. The last experiment was structured using information theory, designing an effective experiment. Four studies were carried out using a number parity decision task, that employed different combinations of cueing Tone (T), Novel (N) and the Goal (G) stimuli. In the first EEG study, contrary to previous findings (Polich 2002, 2007) in control participants, no correlation between the time of a novel condition to the next novel condition and P300 amplitude was found. Therefore single trial across-subject averaging of participants’ data revealed significant correlations (r > .3) of stimulus properties (such as probability, frequency, amplitude and duration) on P300, and even r > .5 was found when N was an environmental sound in schizophrenic patients. In the second EEG study, simultaneously with fMRI recordings, the participants that showed significant behavioural distraction evoked brain activations and differences in both hemispheres (similar to Corbetta, 2002, 2008) while the participants, as a whole, produced significant activations mainly in left cortical and subcortical regions. A context analysis was run in distracted participants contrasting the trials immediately prior to the G trials, resulting in different prefrontal activations, which was consistent with studies of prefrontal control of visual attention (Koechlin 2003, 2007). In the third EEG study, the distractor noise type was manipulated (white vs environmental sounds) as well as presence or absence of scanner background noise in a blocked design. Results showed consistent P300, MMN and RON due to environmental noise. In addition, using time constants found in MEG results (Lu, Williamson & Kaufman, 1992) and adding the CTOA to the analysis, an information theory framework was calculated. After the simulation of the information of the experiment, a saddle indentation in the curve of the information measure based on the states of the incoming signal at around 300 ms CTOA was found. This saddle indentation was evident in more than 60 novel trials. In the fourth study, the CTOA and stimulus properties were manipulated in a parametric experiment. Based on the three studies, reducing complexity if the task (first study), using more than 60 stimuli in the novel conditions (third study). The CTOA randomly varying between 250 ms or 500 ms. Thirty-eight ANCOVA with 2 categorical and 1 continuous regressors were conducted and determined which time and channels elicited reliably signatures (p <.05) in the whole participants at short CTOA. Results revealed differences for the waveforms of current condition by depending on which condition appeared previously as well in terms of frequency and duration in scalp frontal electrodes (such as the second study). These results were interpreted as a consequence of switching between modes of attention and alerting states which resulted in the activation of frontal areas. Moreover, contextual analyses showed that systematic manipulation of stimulus properties allowed the visualization of the relationships between CTOA, executive function and orienting of attention.

Si les régions cérébrales du langage ont étélargement explorées grâce à l’IRM fonctionnelle (IRMf) et la stimulation électrique directe (SED)peropératoire, leur connectivité reste encore incomplètement documentée. Il n’est pas seulement débattuquels faisceaux de SB contribuent au langage, mais également quelle est leur anatomie précise et leur rôlefonctionnel spécifique. Une meilleure compréhension du connectome du langage est requise pourdiminuer la morbidité postopératoire en neurochirurgie et développer de nouveaux traitements cibléspour la rééducation des aphasies. Notre objectif était de cartographier structurellement etfonctionnellement, in vivo, la connectivité du langage. Dans une première étude préclinique portant sur 2Oadultes sains, nous avons combiné des informations structurelles axonales révélées par la tractographieavec des informations fonctionnelles corticales dérivées de l’IRMf (tâche de lecture compréhensive). Huitfaisceaux de SB ont été explorés —i.e. faisceau arqué, faisceau longitudinal supérieur, faisceau frontooccipitalinférieur, faisceau unciné, faisceau longitudinal inférieur, faisceau longitudinal moyen, faisceauoperculo-prémoteur, faisceau frontal transverse—, dont le rôle fonctionnel a été analysé en recherchantune connexion entre leurs terminaisons corticales et les activations IRMf. Les caractéristiquesanatomiques des faisceaux (i.e. volume, longueur, terminaisons corticales), leurs asymétries interhémisphériqueset leurs variations interindividuelles ont été colligées. Ce protocole a permis deconstruire le connectome du langage et d’étudier en détails son organisation structurelle macroscopique.Dans une seconde partie, ces données ont été transposées à la clinique pour le traitement chirurgical depatients souffrant de tumeurs cérébrales (gliomes) en régions du langage. Pendant la résection tumorale,des images de tractographie intégrées à un système de neuronavigation ont été systématiquementcombinées à la SED au cours d’un test de dénomination orale d’images. Ce protocole opératoire a permisd’optimiser les résultats chirurgicaux en termes de qualité d’exérèse et de préservation du langage, et aconstitué une opportunité unique d’étudier en temps réel les corrélations structure – fonction. Encouplant la localisation anatomique précise où chaque SED a été délivrée —obtenue grâce aux images detractographie naviguées— et la sémiologie des paraphasies induites par la SED —colligée par unorthophoniste présent au bloc opératoire—, nous avons déterminé le rôle spécifique de 5 faisceaux tantcortico-corticaux (faisceau arqué, faisceau fronto-occipital inférieur, faisceau frontal transverse) quecortico-sous-corticaux (fibres prémotrices orofaciales, faisceau fronto-striatal) dans différentes souscomposantesdu langage, i.e. traitement phonologique, traitement sémantique, contrôle moteur,planification articulatoire, contrôle exécutif/cognitif de la réponse verbale. Considérés de façon globale,nos résultats permettent d’envisager une meilleure compréhension de l’organisation anatomofonctionnelledes réseaux cérébraux du langage. Au-delà de l’intérêt scientifique, la possibilité deconstruire le connectome du langage spécifique à chaque individu ouvre la voie vers d’importantesapplications en neurochirurgie, dans une perspective de médecine personnalisée. Aujourd’hui, la chirurgiedes tumeurs cérébrales guidée par l’image. Demain, le développement de nouveaux traitements pour larééducation des aphasies, e.g. la déposition ciblée d’agents pharmacologiques, de cellules souches ou deneuromodulations, interagissant directement avec la connectivité résiduelle épargnée par la lésion. / The langage connectome is defined as the neuronal networks that subserve languagefunctions. Anatomically, it comprises specialized cortical areas and modulatory subcortical areas (i.e. deepgray nuclei and cerebellum), as well as their interconnections trough white matter (WM) fascicles.Although brain regions involved in language have been largely explored thanks to functional MRI (fMRI)and intraoprative electrical stimulation (IES), the underlying WM connectivity is still not mastered. It isnot only unknown which WM fascicles specifically contribute to language, but there is also much debateabout their precise anatomy and the functions they subserve during language processing. Betterunderstanding of the structural and functional organization of the language connectome is requisite toreduce postoperative morbidity in neurosurgery and develop targeted treatments for aphasiarehabilitation. Herein, our objective was to map structurally and functionally, in vivo, the subcorticalconnectivity of language. First, we conducted a preclinical study in 20 healthy subjects, combining DTItractography and fMRI (reading comprehension task) to yield connectivity associated with language. Weexplored 8 WM fascicles that have been proposed as putative candidates for language —i.e. arcuatefascicle, superior longitudinal fascicle, inferior fronto-occipital fascicle, uncinate fascicle, inferiorlongitudinal fascicle, middle longitudinal fascicle, operculopremotor fascicle, frontal aslant tract—, towhich we assigned functionality by tracking their connections to the fMRI-derived clusters. We generateda normative database of anatomical characteristics for each WM fascicle, such as volume, length, corticalterminations and their interhemispheric and interindividual variations. By using this construct, weprovided in explicit details the structural map of the language connectome. Second, this body ofknowledge was transposed to brain tumor surgery. Patients suffering of gliomas located close to languageregions were operated on under local anesthesia (i.e. awake surgery) in order to perform intraoperativelanguage mapping (object naming task). Essential language sites were localized through IES andanatomically characterized thanks to navigated tractography images. This intraoperative protocol allowedmaximum tumor resection while preserving language functions. Furthermore, it gave us a uniqueopportunity to perform reliable, real-time structure – function relationships, determining the role of 5WM fascicles (arcuate fascicle, inferior fronto-occipital fascicle, frontal aslant tract, orofacial premotorfibers, frontostriatal fascicle) in different subcomponents of language, i.e. phonological processing,semantic processing, articulatory planning, motor control and executive/cognitive control of verbalresponse. Globally considered, our results allow a better understanding of the anatomo-functionalorganization of the language network in the human brain. Beyond the scientific interest, the possibility toconstruct the individual (patient-specific) connectome paves the way for major applications inneurosurgery, in the perspective of personalized medicine. Today, the maximum safe resection of braintumors located in eloquent language areas, guided by navigated, multimodal images. Tomorrow, thedevelopment of new treatments for rehabilitation of post-stroke aphasia patients, such as the targeteddelivery of drugs, stem cells, or neuromodulation devices, fitting with the residual functional connectivityspared by the lesion.

L'être humain est pourvu des multiples canaux sensoriels par lesquels il appréhende le monde. Un critère fondamental à notre adaptation est notre capacité à établir des relations entre les différentes informations que nos sens perçoivent. Cette capacité est notamment cruciale dans nos interactions sociales puisque nous devons constamment intégrer en une représentation unifiée les informations visuelles (telles que les visages), auditives (telles que les voix) et verbales (telles que le discours ou le nom) afin de pouvoir identifier nos interlocuteurs. Sachant que le traitement des principales informations qui nous permettent d'identifier les personnes (visages, voix et nom de famille) est sous-tendu par l'activation de régions cérébrales spécifiques et distinctes les unes des autres, la question qui se pose est de savoir comment le cerveau opère pour créer une représentation unifiée des personnes que nous connaissons. Dans la première partie de cette thèse, nous passerons en revue différentes études qui ont tenté de cerner les régions cérébrales impliquées dans le traitement (perception et reconnaissance) de chaque type d'information. Le premier chapitre sera consacré aux corrélats cérébraux du traitement des visages, le second à ceux impliqués dans le traitement des noms propres, le troisième à ceux impliqués dans le traitement des voix. Ces processus seront chaque fois abordés sous l'angle de la neuropsychologie cognitive, de l'imagerie cérébrale fonctionnelle et de l'électrophysiologie. Un quatrième chapitre théorique sera consacré à l'étude des processus associatifs entre ces trois types d'informations, et nous verrons que rares sont les études qui ont directement examiné les activités cérébrales spécifiques à la récupération d'associations entre informations relatives à l'identité des personnes. L'approche expérimentale sera abordée dans la seconde partie de cette thèse. Les quatre études décrites dans cette partie se basent sur les résultats de l'étude de Campanella et al. (2001) qui, par PET-scan, ont examiné les régions cérébrales activées par la récupération d'associations entre visages et noms propres. Utilisant la méthode soustractive, consistant en la soustraction de deux conditions unimodales d'une condition bimodale, ces auteurs ont montré une activation d'un réseau d'aires cérébrales latéralisé dans l'hémisphère gauche et incluant notamment le lobule pariétal inférieur, interprété comme étant une région de convergence multimodale où s'opère l'intégration des différentes informations perçues par les sujets. La méthode soustractive sera utilisée dans toutes les expériences décrites dans cette section. La première étude de cette thèse, utilisant la même méthodologie appliquée à la méthode électrophysiologique des potentiels évoqués, aura pour but d'examiner le décours temporel des activités observées par Campanella et al. (2001). La seconde étude en potentiels évoqués aura pour but d'examiner si les activités observées dans les deux études pré-citées sont spécifiques aux processus associatifs entre visages et noms propres, ou s'ils reflètent des processus plus généraux permettant de lier tout objet visuel à son nom. Les études 3 et 4 viseront quant à elles à définir si le lobule pariétal inférieur gauche est impliqué dans l'intégration de stimulations exclusivement visuelles, ou si il est impliqué dans le « binding » de tout type d'information relative aux personnes, quelle que soit les modalités de présentation. Dans ce cadre, l'étude 3 examinera les corrélats cérébraux impliqués dans la récupération d'associations entre visages et voix. L'étude 4 examinera cette question au moyen de l'imagerie par résonance magnétique fonctionnelle. La dernière partie de cette thèse sera consacrée à l'interprétation de l'ensemble des résultats des 4 expériences décrites précédemment. L'accent y sera mis sur la latence d'apparition des ondes spécifiques aux conditions associatives, apparaissant en même temps que les activités propres au traitement de chaque type d'information, ainsi que sur le rôle du gyrus pariétal inférieur gauche dans l'intégration des représentations des différents attributs par lesquels nous identifions les personnes.

La Teoria della Mente (ToM) capacità di rappresentarsi gli stati mentali propri e altrui e di farvi riferimento per prevedere e spiegare il comportamento proprio e altrui riveste un ruolo fondamentale nelle interazioni sociali per un efficace adattamento all'ambiente. Dopo essere stata a lungo indagata in età evolutiva, recentemente la ricerca sulla ToM ha effettuato uno shifting verso fasi successive del ciclo di vita (età adulta ed età anziana) aprendo un nuovo filone di studio in prospettiva life-span. Oggetto della presente tesi di dottorato è lo studio della ToM in prospettiva life-span con tre obiettivi: (1) studiare l'evoluzione della ToM in età adulta e le sue possibile relazioni con la capacità di decision-making, anch'essa dall'alto valore adattivo; (2) studiare la possibile involuzione della ToM in età anziana in condizioni di normalità e di patologia (mild-Alzheimer's disease); (3) indagare i correlati neurali della ToM con metodiche di neuroimaging (fMRI) in soggetti adulti, anziani sani e anziani clinici (Mild Cognitive Impairment, MCI). Le tre ricerche empiriche condotte nella presente tesi di dottorato hanno consentito di rilevare rispettivamente che: (1) la ToM è altamente implicata nei processi di decision-making in età adulta; (2) la ToM subisce una involuzione nei soggetti anziani clinici sin dai livelli più semplici di tale abilità; (3) i circuiti neurali della ToM inizierebbero a mostrare una parziale deattivazione in soggetti anziani clinici rispetto a soggetti di controllo anziani e adulti. / Theory of Mind (ToM) the ability to meta-represent self and others' mental states and to refer to them to foresee and explain the behaviour plays a crucial role in social interactions to provide a successful adaptation to the environment. After being extensively studied in developmental psychology, the research on ToM has recently undergone a shifting towards other life-ages (adulthood and elderly) thus opening a new field if research in a life-span perspective. The object of this PhD thesis is to study of ToM in a life-span perspective with three goals: (1) to study ToM evolution in adult age and to discover its possible relations with the ability of decision-making, which has a major adaptive role as well; (2) to study the possible decay of ToM in old age in normal and clinical conditions (mild-Alzheimer's disease); (3) to study the neural circuits of ToM with neuroimaging methods (fMRI) in adults, healthy old subjects and clinical old subjects (Mild Cognitive Impairment, MCI). The three empiric researches carried on for this PhD thesis provided the following major findings: (1) ToM is highly involved in decision-making processes in adult age; (2) ToM undergoes a decay in clinical old subjects with onset from very simple levels of this ability; (3) ToM neural circuits seem to show a partial deactivation in clinical old subjects and not in healthy old and adult controls.

The side-effects of chemotherapy treatment are an increasingly important research focus as more cancer patients are reaching survivorship. While treatment allows for survival, it can also lead to problems which can significantly affect quality of life. Cognitive impairments after chemotherapy treatment are one such factor. First presented as anecdotal patient reports, over the last decade empirical evidence for this cognitive concern has been obtained. Much attention has been focused on post-chemotherapy research, yet little attention has been granted to these same patients’ cognition before treatment commences. Breast cancer (BC) patients face many obstacles before chemotherapy treatment such as: surgery and side-effects of anesthesia, increased cytokine activity, stress of a new disease diagnosis and upcoming challenges, and emotional burdens such as depression and anxiety. Many of these factors have independently been shown to affect cognitive abilities in both healthy populations as well as other patient groups. Therefore, the pre-treatment (or baseline) BC patient status warrants systematic study. This would then reduce mistakenly attributing carried-over cognitive deficits to side effects of chemotherapy. As well, it is possible that certain confounding variables may have neural manifestations at baseline that could be exacerbated by chemotherapy agents. The following thesis first presents a review paper which critically describes the current literature examining chemotherapy-related cognitive impairments (CRCIs), as well as possible confound variables affecting this population. Subsequently, three original research papers present pre-chemotherapy data showing significant neuroanatomical and neurofunctional differences in BC patients compared to controls. In particular, these neural differences are present in brain regions that have been reported in post-chemotherapy papers. This, as well as the effects of variables such as the number of days since surgery, depression and anxiety scores and more, support the initiative that research attention should increase focus on these patients at baseline in order to better understand their post-chemotherapy results.

The side-effects of chemotherapy treatment are an increasingly important research focus as more cancer patients are reaching survivorship. While treatment allows for survival, it can also lead to problems which can significantly affect quality of life. Cognitive impairments after chemotherapy treatment are one such factor. First presented as anecdotal patient reports, over the last decade empirical evidence for this cognitive concern has been obtained. Much attention has been focused on post-chemotherapy research, yet little attention has been granted to these same patients’ cognition before treatment commences. Breast cancer (BC) patients face many obstacles before chemotherapy treatment such as: surgery and side-effects of anesthesia, increased cytokine activity, stress of a new disease diagnosis and upcoming challenges, and emotional burdens such as depression and anxiety. Many of these factors have independently been shown to affect cognitive abilities in both healthy populations as well as other patient groups. Therefore, the pre-treatment (or baseline) BC patient status warrants systematic study. This would then reduce mistakenly attributing carried-over cognitive deficits to side effects of chemotherapy. As well, it is possible that certain confounding variables may have neural manifestations at baseline that could be exacerbated by chemotherapy agents. The following thesis first presents a review paper which critically describes the current literature examining chemotherapy-related cognitive impairments (CRCIs), as well as possible confound variables affecting this population. Subsequently, three original research papers present pre-chemotherapy data showing significant neuroanatomical and neurofunctional differences in BC patients compared to controls. In particular, these neural differences are present in brain regions that have been reported in post-chemotherapy papers. This, as well as the effects of variables such as the number of days since surgery, depression and anxiety scores and more, support the initiative that research attention should increase focus on these patients at baseline in order to better understand their post-chemotherapy results.