A depressão periparto (PPD) é subtipo altamente prevalente e subdiagnosticado do transtorno depressivo maior (MDD), e causa um importante sofrimento para a mulher, sua família e seu filho. Uma interação complexa entre hormônios, neurotransmissores e fatores genéticos e ambientais pode estar envolvida na etiologia da PPD. Contudo, estudos de neuroimagem na PPD ainda são escassos, particularmente os que identificam alterações neuroquímicas. Sabe-se que a região do córtex pré frontal dorsolateral (dlPFC) está relacionada à funções executivas no circuito pré frontal, e juntamente com o giro do cíngulo anterior (ACG) faz parte das vias neuronais envolvidas no processamento emocional, desde a geração, regulação e reavaliação do estado afetivo. Existem evidências de que ambas as áreas estejam disfuncionais na MDD. A avaliação neuroquímica obtida pela espectroscopia de próton por ressonância magnética (MRS) permite inferir o metabolismo, a neurotransmissão e a viabilidade do tecido neuronal de interesse destas áreas fronto-límbicas. Objetivo: comparar puérperas com depressão periparto (grupo PPD) com puérperas saudáveis (grupo HP) quanto à avaliação neuroquímica no dlPFC esquerdo e no ACG bilateral. Métodos: 36 puérperas do grupo PPD e 25 puérperas do grupo HP foram submetidas à duas entrevistas psiquiátricas estruturadas e à aplicação de questionários e escalas psicométricas, sendo a segunda avaliação realizada seccionalmente à MRS. A MRS foi adquirida pro MRI com campo de 3 Tesla, estando o volume de interesse (VOI) posicionado no dlPFC esquerdo e no ACG bilateral e processada pelo software LCModel. Os resultados neuroquímicos expressos em valores absolutos e normalizados pela creatina (razão metabólito/creatina) foram analisados por ANCOVA, incluindo a idade, o tempo de puerpério e o tipo de contraceptivo, enquanto covariáveis. Resultados: No dlPFC, o grupo PPD apresentou menores valores de Glu/Cr (-0,17; p=0,05), Glx (-0,95 mM; p=0,04), Glx/Cr (-0,22; p=0,03), NAA (-0,60 mM; p<0,01), e NAA/Cr (-0,13; p=0,02) em relação ao grupo HP. No ACG, o uso de hormônios contraceptivos somente com progestágenos resultou em um aumento dos valores de Glu (2,18 mM; p=0,03), Glx (1,84 mM; p=0,03), e redução de Cho/Cr (-0,08; p=0,03) quando comparados ao grupo que não utilizou somente progestágenos, independentemente dos grupos HP e PPD. Conclusão: Os níveis reduzidos de Glu e NAA no grupo PPD estão relacionados, respectivamente, à disfunção metabólica glutamatérgica e neuroglial no dlPFC, o que pode explicar sintomas cognitivos também relacionados à PPD, tal como já verificado no MDD. O uso de hormônios contraceptivos com progestágenos isoladamente interferiu com a neuroquímica do ACG, mas não se relacionou com a PPD. Embora o aumento do glutamato possa sugerir uma hiperfuncionalidade do ACG, e a redução da Cho/Cr representar diminuição de \"turnover\" da membrana lipídica ou da transdução sináptica, seu significado clínico e fisiopatológico ainda é incerto. Estes resultados contribuem com a compreensão dos substratos neuroquímicos de PPD / Peripartum depression (PPD) is a highly prevalent subtype of major depressive disorder (MDD) related to a significant loss for mother, family and baby. An Interaction between hormones, genetic, and environmental factors must be involved in its etiology. However, neuroimaging studies on PPD are still rare, particularly those that identify neurochemical changes. However, neuroimaging studies in PPD are still rare, particularly those that identify neurochemical changes. It is known that the region of the dorsolateral prefrontal cortex (dlPFC) is related to executive functions in the prefrontal circuit, and together with the anterior cingulate gyrus (ACG) is part of the neural pathways involved in emotional processing, including the generation, regulation, and reappraisal of affective state. And, there is evidence that both areas are dysfunctional in MDD. The neurochemical evaluation obtained by spectroscopy of proton magnetic resonance (MRS) allows to infer metabolism, neurotransmission and the viability of the neuronal tissue of interest these frontal-limbic areas. Objective: Compare postpartum women with peripartum depression (PPD group) with healthy postpartum women (HP group) regarding the neurochemical evaluation in the left dlPFC and bilateral ACG. Methods: 36 postpartum women of PPD group and 25 postpartum women of the HP group were subjected to two structured psychiatric interviews and questionnaires and psychometric scales, with the second evaluation performed sectionally at MRS. The MRS was obtained by 3-T MRI system with the volume of interest (VOI) positioned on the left dlPFC and bilateral ACG and processed by LC Model software. The neurochemical results expressed in absolute values and normalized by creatine (reason metabolite/creatine) were analyzed using ANCOVA, including age, postpartum time, the type of contraceptive as covariates. Results: In the dlPFC, PPD group presented significantly lower values of Glu/Cr (-0.17; p=0.05), Glx (-0.95mM; p=0.04), Glx/Cr (-0.22; p=0.03), NAA (-0.60mM; p<0.01), and NAA/Cr (-0.13; p=0.02) than HP. In ACG, progestogens isolated contraceptive hormones use resulted in significantly increased Glu (2.18mM; p=0.03), Glx (1.84mM; p=0.03), and reduced Cho/Cr (-0.08; p=0.03), compared to women without use them, regardless of diagnostic groups. Conclusions: The reduced levels of Glu and NAA in the PPD group are related respectively to the glutamatergic and neuroglial metabolic dysfunction in the dlPFC, which may explain cognitive symptoms also related to PPD as already verified in MDD. Progestogens isolated contraceptive hormones use interfered with neurochemistry of ACG, but not associated with PPD. Although the increase of glutamate may suggest an overactive ACG, and lower Cho/Cr represent decrease of the lipid membrane turnover or synaptic transduction its clinical and pathophysiological significance remains uncertain. These results contribute to the understanding of the neurochemical substrates of PPD

Background: Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. Methods: A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. Principal Findings: The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. Conclusions: The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the psychopathology.

Specific phobia of the animal subtype has been employed as a model disorder exploring the neurocircuitry of anxiety disorders, but evidence is lacking whether the detected neural response pattern accounts for all animal subtypes, nor across other phobia subtypes. The present study aimed at directly comparing two subtypes of specific phobia: snake phobia (SP) representing the animal, and dental phobia (DP) representing the blood-injection-injury subtype. Using functional magnetic resonance imaging (fMRI), brain activation and skin conductance was measured during phobogenic video stimulation in 12 DP, 12 SP, and 17 healthy controls. For SP, the previously described activation of fear circuitry structures encompassing the insula, anterior cingulate cortex and thalamus could be replicated and was furthermore associated with autonomic arousal. In contrast, DP showed circumscribed activation of the prefrontal and orbitofrontal cortex (PFC/OFC) when directly compared to SP, being dissociated from autonomic arousal. Results provide preliminary evidence for the idea that snake and dental phobia are characterized by distinct underlying neural systems during sustained emotional processing with evaluation processes in DP being controlled by orbitofrontal areas, whereas phobogenic reactions in SP are primarily guided by limbic and paralimbic structures. Findings support the current diagnostic classification conventions, separating distinct subtypes in DSM-IV-TR. They highlight that caution might be warranted though for generalizing findings derived from animal phobia to other phobic and anxiety disorders. If replicated, results could contribute to a better understanding of underlying neurobiological mechanisms of specific phobia and their respective classification.

Les fonctions exécutives (FE), et en particulier le Contrôle Inhibiteur (CI), jouent un rôle très important dans la réussite académique et professionnelle ainsi que dans la physiopathologie de nombreux troubles psychiatriques. L'adolescence est une période critique du développement du CI, ce dernier étant sous-tendu en particulier par la maturation tardive du cortex préfrontal jusqu’au début de l'âge adulte. Le premier objectif de cette thèse a été de cartographier les bases neurales du CI durant le développement et d'en évaluer leurs spécificités en les comparant avec celles de la mémoire de travail (MdT), une autre composante clef des FE. À partir d'une méta-analyse des études en IRMf du CI et de la MdT incluant 845 enfants, 1377 adolescents et 10235 adultes, nous avons identifié des modifications de l'activité fonctionnelle, à savoir le passage d'un réseau diffus à un réseau focal plus spécialisé avec l'âge, en accord avec un modèle dynamique du développement cérébral. Un large recouvrement de régions fronto-pariétales pour le CI et la MdT a également été détecté, ce qui soulève la question de la spécificité des processus et des tâches de ces deux FE. Par la suite, nous avons analysé l'effet à long terme du neuro-développement précoce sur le CI à partir de l'étude de la morphologie sulcale, un paramètre anatomique du cerveau déterminé lors de la vie fœtale. Dans un premier temps, nous avons montré, d'après une analyse longitudinale de 243 IRM, la stabilité du motif des sillons durant le développement. Nous avons par la suite établi que les polymorphismes sulcaux du cortex cingulaire antérieur et du sillon frontal inférieur contribuaient, de manière complémentaire, à l'efficience du CI chez l'enfant et également chez l'adulte. Enfin, nous nous sommes intéressés à l’entraînement cognitif au CI à l'adolescence, une période de très grande plasticité cérébrale et de sensibilité à l'environnement. Nous avons étudié chez 49 adolescents de 16-17 ans l'effet d'un entraînement intensif sur tablette tactile (25 sessions de 15 minutes par jour) au CI versus Contrôle Actif aux niveaux cognitif et cérébral (IRMf : tâches de stop-signal, de matrice de points, du réseau attentionnel et de gratification retardée). Nous avons en particulier évalué l'effet des facteurs neurodéveloppementaux précoces sur la réceptivité à l’entraînement au CI. Ces travaux s'inscrivent dans un nouveau champ de recherche interdisciplinaire à l'interface entre les neurosciences et la psychologie. Dans une perspective translationnelle éducative et thérapeutique, il vise à évaluer le plus finement possible, grâce à l'imagerie cérébrale anatomique et fonctionnelle, quelles interventions pédagogiques et thérapeutiques sont susceptibles d'aider au mieux le cerveau à surmonter des difficultés d'ordre cognitif. / Executive functions (EF), including Inhibitory Control (IC), play a major role in academic and professional achievement, as well as in the pathophysiology of many psychiatric disorders. Adolescence is a critical period in IC development as it is underlain by the protracted maturation of prefrontal cortex until early adulthood. The first objective of this thesis was to examine the neural bases of IC during development and to evaluate their specificities by comparing them with the working memory (WM), another key component of EF. Based on a meta-analysis of IC and WM fMRI studies including 845 children, 1377 adolescents and 10235 adults, we identified changes in functional activity with a shift from a diffuse to a more focal and specialized network with age. These results support the model of dynamic neurofunctional development. Moreover, a large overlap of fronto-parietal regions was found for IC and WM, which raises issues regarding the specificities of IC and WM processes and tasks. Second, we analyzed the long-term effect of early neurodevelopment on IC based on the sulcus morphology, an anatomical brain feature determined during fetal life. We showed, using a longitudinal analysis of 243 MRIs, that folding patterns are fixed from childhood to adulthood. Subsequently, we established that the sulcal polymorphisms of the anterior cingulate cortex and the inferior frontal sulcus complementary contributed to IC efficiency in both children and adults. Finally, we studied IC training in adolescence, a period of high brain plasticity and environmental sensitivity. We examined the effects of an intensive IC training (25 sessions of 15 minutes per day) versus active control training group on touchscreens in 49 adolescents (16-17 years-old) on cognitive and brain levels (fMRI: stop-signal, dot matrix, attentional network and delayed gratification tasks). We also assessed the effect of early neurodevelopmental factors on IC training receptivity. This thesis is part of a new field of interdisciplinary research, at the interface between neurosciences and psychology. It includes translational educational and therapeutic perspectives, with aims at evaluating as finely as possible, using anatomical and functional brain imaging, what pedagogical and therapeutic interventions are likely to help the brain to overcome cognitive difficulties.

No description available.

Les pilotes d'avion sont constamment confrontés à des situations où ils doivent traiter des quantités importantes de données en très peu de temps, ce qui peut conduire à des erreurs. Nous avons créé un système de détection des écarts capable d'auditer le cockpit en temps réel pour détecter les actions qui ont été incorrectement ajoutées, omises ou qui n'ont pas été effectuées dans le bon ordre. Ce modèle évalue les écarts en se basant sur les données hiérarchiques des tâches trouvées dans le modèle de référence ontologique pour les procédures de pilotage, qui contient des procédures de référence basées sur la connaissance et rassemblées par des experts dans le domaine. Les actions des pilotes sont comparées aux séquences de référence de l'ontologie à l'aide de l'algorithme Needleman-Wunsch pour l'alignement global, ainsi que d'un réseau LSTM siamois. Une API pouvant être étendue à plusieurs simulateurs aérospatiaux, ainsi qu'un Runner, ont été créés pour permettre au Deviation Framework de se connecter au simulateur XPlane afin de surveiller le système en temps réel. Des données créées synthétiquement et contenant des mutations de séquences ont été analysées à des fins de test. Les résultats montrent que ce cadre est capable de détecter les erreurs ajoutées, omises et hors séquence. En outre, les capacités des réseaux siamois sont exploitées pour comprendre la relation de certaines anomalies de la chaîne de séquence afin qu'elles puissent être correctement ignorées (comme certaines tâches qui peuvent être exécutées dans le désordre par rapport à la séquence de référence). Les environnements de simulation enregistrant les données à une fréquence de 10 Hz, une valeur de 0.1 seconde constitue notre référence en temps réel. Ces évaluations de déviation peuvent être exécutées plus rapidement que notre contrainte de 0,1 seconde et ont été réalisées en 0,0179 seconde pour une séquence de décollage contenant 23 actions, ce qui est nettement plus performant que les modèles suivants de l'état de l'art. Les résultats de l'évaluation suggèrent que l'approche proposée pourrait être appliquée dans le domaine de l'aviation pour aider à détecter les erreurs avant qu'elles ne causent des dommages. \\En outre, nous avons formé un modèle d'apprentissage automatique pour reconnaître les signaux de pré-erreur dans le cortex cingulaire antérieur (CCA) à l'aide des données de test Flanker de l'ensemble de données COG-BCI, qui peuvent ensuite être utilisées pour détecter les états de pré-erreur chez les pilotes d'avion. Divers modèles d'apprentissage automatique ont été appliqués à l'ensemble de données, notamment des machines à vecteurs de support (SVM), des forêts aléatoires, un double modèle de réseau neuronal convolutif (CNN) et un modèle Transformer. Au-delà des conclusions typiques de l'étude, notre objectif s'étend à l'évaluation de l'applicabilité du modèle dans un domaine secondaire, à savoir l'évaluation du pouvoir discriminant des classificateurs pendant les procédures de décollage pour les pilotes d'avion. Les résultats de l'analyse de l'ensemble de données FLANKER ont révélé la supériorité du modèle transformateur, avec des réductions notables des faux négatifs et un score final macro moyen F1 de 0,610, et un score final macro moyen F1 de 0,578 sur les données pilotes. Comme nous prévoyons une augmentation des performances du classificateur avec davantage de données d'entraînement et des bandes d'interrogation étendues, cette étude jette les bases d'une recherche plus poussée sur la prédiction des états erronés et les modèles d'optimisation de l'apprentissage automatique pour les ICB et les applications du monde réel. / Aircraft pilots are constantly undergoing situations where they must process significant amounts of data in very small periods of time, which may lead to mistakes. We have created a deviation detection system that is capable of auditing the cockpit in real time to detect actions that have been incorrectly added, omitted, or done out of sequence. This model assesses deviations based on hierarchical task data found in the Ontological Reference Model for Piloting Procedures, which contains knowledge-based reference procedures assembled by experts in the domain. Pilot actions are compared to ontology reference sequences using the Needleman-Wunsch algorithm for global alignment, as well as a Siamese LSTM network. An API that can be expanded to several Aerospace Simulators, as well as a Runner, was created to enable the Deviation Framework to connect to the XPlane simulator for real-time system monitoring. Synthetically created data containing sequence mutations were analyzed for testing. The results show that this framework is capable of detecting added, omitted, and out of sequence errors. Furthermore, the capabilities of Siamese networks are leveraged to understand the relation of certain sequence chain anomalies so that they can correctly be ignored (such as certain tasks that can be performed out of order from the reference sequence). With simulation environments recording data at a frequency of 10Hz, a value of 0.1 seconds is our real-time benchmark. These deviation assessments are capable of being run faster than our 0.1 second requirement and have been clocked at 0.0179 seconds for one Takeoff sequence containing 23 actions - significantly outperforming the next state of the art models. The evaluation results suggest that the proposed approach could be applied in aviation settings to help catch errors before harm is done. \\Moreover, we have trained a machine learning model to recognize pre-error signals in the anterior cingulate cortex (ACC) using Flanker test data from the COG-BCI dataset, which can be subsequently employed to detect pre-error states in aviation pilots. Various machine learning models were applied to the dataset, including Support Vector Machines (SVM), Random Forests, double Convolutional Neural Network (CNN) model, and a Transformer model. Moving beyond typical study conclusions, our objective extends to assessing model applicability in a secondary domain —evaluating the classifiers' discriminative power during takeoff procedures for aviation pilots. Results from the analysis of the FLANKER dataset revealed the superiority of the transformer model, with notable reductions in false negatives and a final macro averaged F1 score of 0.610, and a final macro averaged F1 of 0.578 on the Pilot data. As we anticipate increases in classifier performance with more training data and extended polling bands, this study lays the groundwork for further research in erroneous state prediction and machine learning optimization models for BCI and real-world applications.

A inferência do curso temporal da atividade neural a partir do efeito BOLD é um importante problema, ainda em aberto. A forma da curva BOLD não reflete diretamente as características temporais da atividade eletrofisiológica dos neurônios. Nessa tese, é introduzido o conceito de tempo de processamento neural (TPN) como um dos parâmetros do modelo biofísico da função de resposta hemodinâmica (HRF). O objetivo da introdução desse conceito é obter estimativas mais acuradas da duração da atividade neural a partir do efeito BOLD, que possui auto grau de nãolinearidade. Duas formas de estimar os parâmetros do modelo do efeito BOLD foram desenvolvidas. A validade e aplicabilidade do conceito de TPN e das rotinas de estimação foram avaliadas por simulações computacionais e análise de séries temporais experimentais. Os resultados das simulações e da aplicação foram comparados com medidas da forma da HRF. O experimento analisado consistiu em um paradigma de tomada de decisão na presença de distratores emocionais. Esperase que o TPN em áreas sensoriais primárias seja equivalente ao tempo de apresentação de estímulos. Por outro lado, o TPN em áreas relacionadas com a tomada de decisão deve ser menor que a duração dos estímulos. Além disso, o TPN deve depender da condição experimental em áreas relacionadas ao controle de distratores emocionais. Como predito, o valores estimados do TPN no giro fusiforme foram equivalentes à duração dos estímulos e o TPN no giro do cíngulo dorsal variou com a presença de distrator emocional. Observou-se ainda lateralidade do TPN no córtex pré-frontal dorsolateral. As medidas da forma da HRF obtidas por um método convencional não dectectaram as variações observadas no TPN / The extraction of information about neural activity dynamics related to the BOLD signal is a challenging task. The temporal evolution of the BOLD signal does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. We describe two routines to estimate the parameters of the HRF model. The face validity and applicability of the concept of NPT and the estimation procedures are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. We analysed an experiment based on a decision-making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas is approximately the stimulus presentation duration. On the other hand, the NPT in brain areas related to decisionmaking processes should be less than the stimulus duration. Moreover, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the estimated NPTs in the dorsolateral prefrontal cortex indicate functional laterality of this region. The analysis using standard measures of HRF did not detect the variations observed in our method (NPT)

This thesis extends the understanding of the neural and neurochemical contributions to two forms of behavioural adaptation, reversal learning and contingency degradation, in which stimulus/action-reward contingencies are altered. The results are interpreted within the psychological framework of the compulsivity construct, and their implications for the pathological behaviour of obsessive-compulsive-disorder (OCD) are considered. The orbitofrontal cortex (OFC) and striatum are key brain structures involved in reversal learning, as are the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) within those respective regions. However, there has been little empirical evidence of how these two structures and neurochemical systems interact, especially in the functional context of reversal learning. In Chapter Three, the impact of experimentally-induced reductions of 5-HT in the anterior OFC on monoamine levels in subcortical structures such as the striatum and amygdala was determined, DA being found to be significantly up-regulated in the amygdala. Functionally, 5-HT depletion of the OFC has previously been shown to induce deficits in reversal learning. To determine the possible causal significance of amygdala dopamine up-regulation for said reversal learning deficit, the effects of blocking the upregulation with the infusion of intra amygdala DA receptor antagonists following bilateral OFC 5-HT depletion were investigated in a reversal learning paradigm. In Chapter Four, the differential roles of regions of striatum were examined in visual reversal learning. Two recent investigations in non-human primates highlighted the role of the striatum in reversal learning,but pinpointed the critical region to be either the ventromedial caudate or the putamen. Marmosets were trained on a serial reversal task that allowed multiple acute neural manipulations, and the ventromedial caudate and putamen were then reversibly inactivated using the GABAA agonist muscimol. Results indicated dose-related impairments specifically in reversal learning within the putamen, with sparing of discrimination retention. By contrast, similar reversible inactivation of the caudate nucleus produced marked deficits in visual discrimination performance (retention). In Chapter Five, the neural basis of action-outcome contingency knowledge was investigated by inactivating distinct regions of the PFC, the perigenual ACC (pgACC; area 32) and the anterior OFC, and determining response sensitivity to the degradation of action-outcome contingencies. In previous work, excitotoxic lesions of either the pgACC or the OFC had been found to induce insensitivity to contingency degradation in marmosets. However, the design of that experiment did not allow specification of whether stimulus- or action-outcome associations were disrupted, and a precise neural locus could not be determined for the behavioural effects as the OFC lesions included parts of the lateral and medial OFC. I therefore developed a novel contingency degradation paradigm that distinguished between stimulus- and action-outcome associations to enable the study of acute pharmacological manipulations in both brain regions. The pgACC and OFC were reversibly inactivated using GABAA-GABAB agonists (muscimol-baclofen). Whereas the pgACC inactivation produced selective deficits in sensitivity to action-outcome contingency degradation, OFC inactivation reduced the suppressive effect of noncontingent reward on responding more generally but left intact sensitivity to degradation of the contingencies. These results are discussed in terms of different theories of the functions of the pgACC and OFC. In the final discussion the findings on the neural substrates of reversal learning and contingency degradation are drawn together in terms of their significance for theories of PFC involvement in cognitive control, and for the understanding of OCD and other neuropsychiatric disorders.

No description available.

A inferência do curso temporal da atividade neural a partir do efeito BOLD é um importante problema, ainda em aberto. A forma da curva BOLD não reflete diretamente as características temporais da atividade eletrofisiológica dos neurônios. Nessa tese, é introduzido o conceito de tempo de processamento neural (TPN) como um dos parâmetros do modelo biofísico da função de resposta hemodinâmica (HRF). O objetivo da introdução desse conceito é obter estimativas mais acuradas da duração da atividade neural a partir do efeito BOLD, que possui auto grau de nãolinearidade. Duas formas de estimar os parâmetros do modelo do efeito BOLD foram desenvolvidas. A validade e aplicabilidade do conceito de TPN e das rotinas de estimação foram avaliadas por simulações computacionais e análise de séries temporais experimentais. Os resultados das simulações e da aplicação foram comparados com medidas da forma da HRF. O experimento analisado consistiu em um paradigma de tomada de decisão na presença de distratores emocionais. Esperase que o TPN em áreas sensoriais primárias seja equivalente ao tempo de apresentação de estímulos. Por outro lado, o TPN em áreas relacionadas com a tomada de decisão deve ser menor que a duração dos estímulos. Além disso, o TPN deve depender da condição experimental em áreas relacionadas ao controle de distratores emocionais. Como predito, o valores estimados do TPN no giro fusiforme foram equivalentes à duração dos estímulos e o TPN no giro do cíngulo dorsal variou com a presença de distrator emocional. Observou-se ainda lateralidade do TPN no córtex pré-frontal dorsolateral. As medidas da forma da HRF obtidas por um método convencional não dectectaram as variações observadas no TPN / The extraction of information about neural activity dynamics related to the BOLD signal is a challenging task. The temporal evolution of the BOLD signal does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. We describe two routines to estimate the parameters of the HRF model. The face validity and applicability of the concept of NPT and the estimation procedures are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. We analysed an experiment based on a decision-making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas is approximately the stimulus presentation duration. On the other hand, the NPT in brain areas related to decisionmaking processes should be less than the stimulus duration. Moreover, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the estimated NPTs in the dorsolateral prefrontal cortex indicate functional laterality of this region. The analysis using standard measures of HRF did not detect the variations observed in our method (NPT)