O núcleo pré-mamilar dorsal (PMd), de crucial importância para expressão do comportamento de defesa exibido por roedores durante o confronto com predador natural, odor ou contexto associado, representa o sítio hipotalâmico com maior aumento no número de células imunorreativas a proteína Fos após o confronto predatório. Estudos mostram que a mediação noradrenérgica central é crítica para a expressão das respostas de medo e que tanto as respostas incondicionadas como as contextuais ao odor do gato dependem de sua ação central, mediada pelo PMd. Dada a importância da modulação noradrenérgica no PMd para a expressão das respostas anti-predatórias, investigamos quais grupamentos catecolaminérgicos aferentam o núcleo empregando técnicas de rastreamento retrógrado somado a técnica de imunofluorescência (dupla-marcação). Nossos resultados revelaram que a única fonte de aferência catecolaminérgica para o PMd é oriunda do locus ceruleus, onde encontramos um número conspícuo de células duplamente marcadas, indicando ser este o responsável pelo suporte noradrenérgico ao PMd. / Evidence suggests the medial hypothalamic defensive system plays a pivotal role in processing of predator-derived and contextual-related cues. Fear responses to predatory threats rely heavily on the PMd beta adrenergic neurotransmission. Thus, it has been shown that propranolol significantly reduced PMdFos expression in response to cat odor, and that beta adrenoceptor blockade, in the PMd, reduced defensive responses to both cat odor exposure and cat odor-related context. Given the importance of the noradrenergic innervation of the PMd to the expression of unconditioned and learned fear responses, we have presently investigated the putative noradrenergic source of inputs to the nucleus. To this end, we have combined Fluoro-Gold retrograde tract-tracing and catecholamine immunostaining, and found that the locus ceruleus is seemingly the only source of catecholaminergic source of inputs to the PMd. In addition, the present findings are particularly interesting given the well-documented roles of the locus ceruleus roles in attentional processes.

Orientador: Mateus Borba Cardoso / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-09-05T14:11:53Z (GMT). No. of bitstreams: 1 Vescovi_RafaelFerreiraDaCosta_D.pdf: 72387058 bytes, checksum: 728a9ca57a44975a0fbb2f766a7bbd5c (MD5) Previous issue date: 2017 / Resumo: Esta tese apresentará uma introdução a imagens de raios-x e como adquirir e processar imagens usando linhas de luz síncrotron. Apresentará os desafios matemáticos e técnicos para reconstruir amostras em três dimensões usando a reconstrução de Tomografia Computadorizada, uma técnica conhecida como CT. Esta técnica tem seu campo de visão limitado ao tamanho da câmera e ao tamanho da iluminação. Uma técnica para ampliar esse campo de visão vai ser apresentada e os desafios técnicos envolvidos para que isso aconteça. Um \textit{pipeline} é proposto e todos os algoritmos necessários foram empacotados em um pacote python chamado Tomosaic. A abordagem baseia-se em adquirir tomogramas parciais em posiçoes pré definidas e depois mesclar os dados em um novo conjunto de dados. Duas maneiras possíveis são apresentadas para essa mescla, uma no domínio das projeções e uma no domínio dos sinogramas. Experimentos iniciais serão então usadas para mostrar que o método proposto funciona com computadores normais. A técnica será aplicada mais tarde para pesquisar a anatomia de cérebros de camundongo completos. Um estudo será apresentado de como obter informação em diferentes escalas do cérebro completo do rato utilizando raios-x / Abstract: This thesis will present an introduction to x-ray images and how to acquire and thread images using synchrotron beamlines. It will present the mathematical and technical challenges to reconstruct samples in three dimensions using Computed Tomography reconstruction, a technique known as CT. This technique has a field of view bounded to the camera size and the illumination size. A technique to extended this field of view is going to be presented and the technical challenges involved in order for that to happen will be described. A pipeline is proposed and all the necessary algorithms are contained into a python packaged called Tomosaic. The approach relies on acquired partial tomogram data in a defined grid and later merging the data into a new dataset. Two possible ways are presented in order to that: in the projection domain, and in the sinogram domain. Initial experiments will then be used to show that the pipeline works with normal computers. The technique will be later applied to survey the whole anatomy of whole mouse brains. A study will be shown of how to get the complete range of scales of the mouse brain using x-ray tomography at different resolutions / Doutorado / Física / Doutor em Ciências / 163304/2013-0 / 1247445/2013, 1456912/2014 / CNPQ / CAPES

Esta pesquisa, propondo uma metodologia auxiliar para a disciplina de empreendedorismo originou-se de uma análise mais aprofundada ocorrida dentro da universidade, onde se questiona a falta de efetividade dos conteúdos programáticos e metodologias empregadas na educação empreendedora. De um modo geral as Instituições de Ensino Superior (IES), formam mais futuros empregados que empregadores. Várias instituições oferecem inúmeros cursos e disciplinas de empreendedorismo ou afins, mas continuam colocando no mercado cada vez mais jovens que irão competir à um posto de trabalho por não conseguirem ver o empreendedorismo como opção de carreira. Uma possível resposta estaria associada por fatores identificados em estudos recentes que afirmam que é de suma importância entender melhor como funciona o cérebro dos empreendedores para que se possa oferecer metodologias mais assertivas. Para muitos autores o processo de descoberta de oportunidades de negócios é uma das principais características do comportamento empreendedor e entender como este processo ocorre no cérebro dele abriria novas perspectivas. Esta pesquisa, desenvolvida a partir de dois experimentos, busca contribuir no âmbito universitário com uma proposta metodológica, desenvolvida à luz da neurociência, para a disciplina de Empreendedorismo. No primeiro experimento, denominado de teste piloto, com o objetivo de verificar possíveis padrões nos clusters neurais dos empreendedores, quando identificam uma oportunidade, foi realizado o Mapeamento Cognitivo Cerebral com o uso de eletroencefalograma em 14 indivíduos do sexo masculino, sendo sete “empreendedores estabelecidos” e sete não empreendedores. Os resultados dos testes mostraram que os mapas neurais dos empreendedores sugeriram que as áreas frontais direita e esquerda dos cérebros foram acionadas tanto no momento de descoberta de oportunidades quanto no momento de propensão a assumir riscos, enquanto os não empreendedores mostraram organizações neurais bem distintas durante os dois momentos. Este resultado aliado a outros estudos realizados por pesquisadores de empreendedorismo levou ao segundo experimento: o desenvolvimento de uma proposta metodológica auxiliar, que melhorasse a performance de alunos no processo de identificação de oportunidades de negócios. Esta proposta metodológica, cerne deste estudo, foi apresentada em um objeto de aprendizagem denominado: MADE-PERFIO, Módulo Auxiliar para Disciplina de Empreendedorismo-Performance na Identificação de Oportunidades, um curso de 40 horas, direcionado para melhorar a performance do aluno na identificação de oportunidades. A pesquisa sobre a efetividade da metodologia oferecida através do Módulo foi feita com 45 professores de graduações e de pós graduações e com 50 alunos de pós graduação de diversas faculdades e universidades maranhenses. Através de um curso de capacitação os professores puderam acessar o objeto de aprendizagem, testar a metodologia proposta e desenvolver suas performances cujos resultados foram extremamente encorajadores. Em média, os professores submetidos à nova metodologia melhoraram em 21% suas capacidades em identificarem oportunidades de negócios. Com relação à metodologia apresentada através do MADE-PERFIO, 45% classificaram com o conceito “ótimo” e 40% com o conceito “muito bom”. A metodologia foi apresentada aos alunos no formato de Módulo Auxiliar, pois todos declararam já ter tido contato com a disciplina de Empreendedorismo, mas ainda não haviam empreendido. A pesquisa com os alunos mostrou um acréscimo médio de 23% em suas capacidades de identificarem oportunidades e 65% deles classificaram como “excelente” a relevância do conteúdo. / This research, which proposes an auxiliary method for the entrepreneurship subject, was originated from a more deeply analysis made within the university, where it is argued about the lack of effectiveness in the program contents and methods used in the entrepreneurial education. In general, the higher level educational institutions (IES - Instituições de Ensino Superior) produce more future employees than employers. Several institutions may offer countless entrepreneurial and other related courses and subjects but continue increasingly placing in the labor market the youngsters who will try to find a job instead of starting some entrepreneurship as a career. A possible answer would be associated to factors identified in recent studies that claim to be of utmost importance to better understand how the entrepreneurs' brains work in order to offer more assertive methodologies. For many authors the process of business opportunities discovery is one of the main characteristics of the entrepreneur behavior and new perspectives could be open by understanding how this process works in the brain. The research, developed from two experiments, seeks to contribute in the university field with a methodological proposition to the subject of Entrepreneurship developed by the light of neuroscience. In the first experiment, called pilot test, which had the aim to check eventual standards in the entrepreneurs' neural clusters when they identify an opportunity, it was provided a Cognitive Brain Mapping by using electroencephalogram in 14 male individuals: seven were "established entrepreneurs" and seven were non-entrepreneurs. The test results showed that the entrepreneurs' neural maps suggested that the right front and the left front areas of the brain were set in motion both at the moment the opportunities were discovered and at the moment of taking risks, while non-entrepreneurs showed neural organizations much different in both moments. This result, combined to other studies made by entrepreneurship researchers, led to a second experiment: the development of an auxiliary methodological proposal that could improve the students' performance in the process of identification of business opportunities. This methodological proposal, main objective of this study, was presented in a learning issue called MADE-PERFIO, Módulo Auxiliar para Disciplina de Empeendedorismo-Performance na Identificação de Oportunidades (Auxiliary Module for the Entrepreneurship-Performance Subject to identify Opportunities), a 40-hour course designed to improve the student performance in the opportunities identification process. Research studies on the effectiveness of methodology offered through the Module was made with 45 graduation and post-graduation teachers and with 50 post-graduation students from several colleges and universities of Maranhão. Teachers, by means of a qualification course, had the chance to access the learning object, to test the proposed methodology and develop its performance whose results were thoroughly encouraging.Teachers submitted to the new technology improved in 21% their abilities in the business opportunity identification. With respect to the methodology presented through MADE-PERFIO, 45% considered the concept as "excellent" and 40% as "very good". The methodology was presented to the students in an Auxiliary Module format, since all of them pointed that they had contact with Entrepreneurship course but none had good understanding. Research studies with the students showed an average increase of 23% in their opportunities identification abilities and 65% considered "excellent" on the content of the material showed by MADE-PERFIO.

This study examined the effectiveness of Mind Mapping (a diagram of the structure of ideas in an associative manner, using graphics, color and key words) as a note-taking device in a training course in a large, high-tech corporation, as compared to traditional note-taking. The population for this study consisted of personnel employed by a major high-tech firm, that had voluntarily registered for a Mind Mapping training class. The effect of Mind Mapping was measured by the pre-test and post-test of the control and experimental groups.

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) contrast has become a widespread technique in brain research. The central challenge in fMRI is the detection of relatively small activity-induced signal changes in the presence of various other signal fluctuations. Physiological fluctuations due to respiration and cardiac pulsation are dominant sources of confounding variability in BOLD fMRI. This dissertation seeks to characterize and compensate for non-neural physiological fluctuations in fMRI. First, the dissertation presents an improved and generalized technique for correcting T1 effect in cardiac-gated fMRI data incorporating flip angle estimated from fMRI dataset itself. Using an unscented Kalman filter, spatial maps of flip angle and T1 relaxation are estimated simultaneously from the cardiac-gated time series. Accounting for spatial variation in flip angle, the new method is able to remove the T1 effects robustly, in the presence of significant B1 inhomogeneity. The technique is demonstrated with simulations and experimental data. Secondly, this dissertation describes a generalized retrospective technique to precisely model and remove physiological fluctuations from fMRI signal: Physiological Impulse Response Function Estimation and Correction (PIRFECT). It is found that the modeled long-term physiological fluctuations explained significant variance in grey matter, even after removing short-term physiological effects. Finally, application of the proposed technique is observed to substantially increase the intra-session reproducibility of resting-state networks.

The interplay between sounds and movements is not only critical for music performance, but also for the acquisition of speech, and might underlie the success of using music as a therapeutic tool in the facilitation of movements. This dissertation is comprised of three functional magnetic resonance imaging studies that aim to elucidate the neural basis underlying interactions between the auditory and motor systems in the context of musical rhythm perception and production. Study 1 investigated the neural correlates that facilitate auditory-motor coupling while subjects tapped along with an isochronous rhythm. Auditory input was manipulated so that the metric saliency of the isochronous rhythm increased across five parametric levels in order to modulate subjects’ tapping behaviour. [...] / L’interaction entre le son et le mouvement n’est pas seulement essentielle lors de prestations musicales, mais aussi lors de l’ acquisition de la parole, et pourrait être à la base du succès de la musique lorsqu’elle est utilisée en tant qu’agent thérapeutique visant la facilitation du mouvement. Cette dissertation consiste en trois études d’imagerie par résonance magnétique fonctionnelle visant à élucider les fondements neuraux à la base de l’interaction entre le système auditif et le système moteur dans le contexte de la perception et de la production de rythmes musicaux. La première étude examina les corrélats neuraux facilitant le couplage auditif-moteur chez des sujets produisant des battements alors qu’ils étaient guidés par un rythme isochronique. L’information auditive fut manipulée pour que la proéminence métrique du rythme isochronique augmente à travers cinq niveaux paramétriques dans le but de moduler les battements produits par le sujet. [...]

Background: Functional magnetic resonance imaging (fMRI) can require extensive preprocessing to minimize noise and maximize signal. There is evidence suggesting that fixed-subject preprocessing pipelines, the current standard in fMRI preprocessing, are suboptimal compared to individual-subject pipelines. Aim: We sought to test if individual-subject preprocessing pipeline optimization, compared to fixed, resulted in stronger and more reliable brain-patterns in episodic recognition. Methodology: 27 young healthy controls were scanned via fMRI while performing forced-choice episodic recognition. Several sets of fMRI preprocessing pipelines were tested and optimized in a fixed and individual-subject manner, using methods outlined by Churchill et al. (2011). Results: Individual-subject pipeline optimization, compared to fixed, significantly increased reproducibility, significantly increased the detection of positively and negatively activated voxels, and resulted in a brain-pattern with significant correlation to a task behavioral measure. Conclusions: Individual-subject pipeline optimization, compared to fixed, led to stronger and more reliable brain-patterns that are significantly correlated with behavior.

Background: Functional magnetic resonance imaging (fMRI) can require extensive preprocessing to minimize noise and maximize signal. There is evidence suggesting that fixed-subject preprocessing pipelines, the current standard in fMRI preprocessing, are suboptimal compared to individual-subject pipelines. Aim: We sought to test if individual-subject preprocessing pipeline optimization, compared to fixed, resulted in stronger and more reliable brain-patterns in episodic recognition. Methodology: 27 young healthy controls were scanned via fMRI while performing forced-choice episodic recognition. Several sets of fMRI preprocessing pipelines were tested and optimized in a fixed and individual-subject manner, using methods outlined by Churchill et al. (2011). Results: Individual-subject pipeline optimization, compared to fixed, significantly increased reproducibility, significantly increased the detection of positively and negatively activated voxels, and resulted in a brain-pattern with significant correlation to a task behavioral measure. Conclusions: Individual-subject pipeline optimization, compared to fixed, led to stronger and more reliable brain-patterns that are significantly correlated with behavior.

The identification of eloquent areas is of utmost importance in the surgery of tumors located near speech-eloquent brain areas, since the classical concept of a constant localization was proven to be untrue and the spatial localization of these areas may show large interindividual differences. Some neurosurgical centers apply intraoperative electrophysiological methods that, however, necessitate the performance of surgery in the awake patient. This might be a severe burden both for the patient and the operating team in a procedure that lasts several hours; in addition, electrical stimulation may generate epileptic seizures. Alternatively, methods of functional brain imaging (e.g., PET, fMRI, MEG) may be applied, which allow individual localization of speech-eloquent areas. Matching of these image data with a conventional 3D-CT or MRI now allows the exact transfer of this information into the surgical field by neuronavigation. Whereas standards concerning electrophysiological stimulation techniques that could prevent a permanent postoperative worsening of language are available, until now it remains unclear whether the resection of regions shown to be active in functional brain imaging will cause a permanent postoperative deficit. / Die Identifikation sprachaktiver Areale ist von höchster Bedeutung bei der Operation von Tumoren in der Nähe des vermuteten Sprachzentrums, da das klassische Konzept einer konstanten Lokalisation des Sprachzentrums sich als unrichtig erwiesen hat und die räumliche Ausdehnung dieser Areale eine hohe interindividuelle Varianz aufweisen kann. Einige neurochirurgische Zentren benutzen deshalb intraoperativ elektrophysiologische Methoden, die jedoch eine Operation am wachen Patienten voraussetzen. Dies kann sowohl für den Patienten als auch das Operations-Team eine schwere Belastung bei diesem mehrstündigen Eingriff darstellen, zusätzlich können epileptische Anfälle durch die elektrische Stimulation generiert werden. Alternativ können Modalitäten des «functional brain imaging» (PET, fMRT, MEG usw.) eingesetzt werden, die die individuelle Lokalisation sprachaktiver Areale gestatten. Die Bildfusion dieser Daten mit einem konventionellen 3D-CT oder MRT erlaubt den exakten Transfer dieser Daten in den OP-Situs mittels Neuronavigation. Während Standards bei elektrophysiologischen Stimulationstechniken existieren, die eine permanente postoperative Verschlechterung der Sprachfunktion weitgehend verhindern, bleibt die Relevanz sprachaktiver Areale bei den neuesten bildgebenden Techniken bezüglich einer Operations-bedingten Verschlechterung der Sprachfunktion bisher noch unklar. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

A series of studies is described here which explore the functional organisation of face- and object-processing neurones in the adult vervet monkey brain. This fundamental issue in high-level vision is addressed by the use of a novel molecular mapping technique that was developed for this purpose. / In the first study, the temporal dynamics of c-fos and zif268 expression were delineated in detail in the rat visual cortex. Knowing the precise temporal parameters of up-regulation (after onset of sensory stimulation) and down-regulation (after offset of sensory stimulation) of these genes was integral to optimising the temporal aspects of the stimuli to be used for subsequent mapping experiments. This study provided the critical information for devising stimuli with corresponding temporal parameters to those of c-fos or zif268 so that one could take advantage of the disparity between the expression of their mRNA and protein products in order to visualise activated neurones. / In the second study, the newly developed molecular mapping technique was validated in the rat auditory, visual and multisensory systems. First, bimodal audiovisual stimuli were designed using the data obtained from the first study. Then, through the combined histological detection of the mRNA and protein products of zif268, discrete populations of neurones responsive to either component of the bimodal stimulus were visualised. It was also observed that a third population of neurones was found that responded to the stimulation through both sensory modalities. The combined results from these two studies set the stage for addressing the issue of the organisation of face- and object-selective neurones of the inferior temporal cortex in the vervet monkey brain. / In the third study, the functional organisation of face- and object-selective neurones was examined using the molecular mapping technique. Based on the data gathered from the first two studies, suitable stimuli containing two distinct object classes (conspecific faces and non-face familiar objects) were designed with appropriate temporal parameters. / Finally, the last study provided an opportunity to address the issue of hemispheric asymmetry of function in the context of face processing in the non-human primate brain. Results support the notion that there may indeed be phylogenetic explanations for the hemispheric asymmetry observed in the human brain.