The works presented in this dissertation provide insights into the mechanisms of chemotherapy-induced cognitive impairment (CICI or “ChemoBrain”) and take steps toward outlining a preventive strategy. CICI is now widely recognized as a complication of cancer chemotherapy experienced by a large percentage of cancer survivors. Approximately fifty percent of existing FDA-approved anti-cancer drugs generate reactive oxygen species (ROS). Doxorubicin (Dox), a prototypical ROS-generating chemotherapeutic agent, produces the reactive superoxide radical anion (O2-•) in vivo. Dox treatment results in oxidation of plasma proteins, including ApoA-I, leading to TNF-α-mediated oxidative stress in plasma and brain. TNF-α elevation in brain leads to further central nervous system toxicity including mitochondrial dysfunction, neuronal death, and cognitive impairment. Co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma without interfering with the cancer-killing ability of Dox. In studies presented in this dissertation, we measured oxidative stress in both brain and plasma of Dox-treated mice both with and without MESNA. MESNA ameliorated Dox-induced oxidative protein damage in plasma, confirming our prior studies, and in a new finding led to decreased oxidative stress in brain. Using novel object recognition (NOR), we demonstrated the Dox administration resulted in memory deficits. Using hydrogen magnetic resonance imaging spectroscopy (H1-MRS) techniques, we demonstrated that Dox administration led to a dramatic decrease in choline(phosphocholine)/creatine (Cho/Cr) ratios in mouse hippocampus. The activities of both phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D(PLD) were severely diminished following Dox administration. The activity of PC-PLC was preserved when MESNA was co-administered with Dox. In the absence of TNF-α, MRS-indexed Cho/Cr ratio, PLD activity, and mitochondrial oxygen consumption are preserved in brain, and markers of oxidative stress are reduced. Together with results from our previous studies, these results provide strong evidence that TNF-α is strongly associated, if not responsible for CICI. We also tested the notion that O2-• is responsible for Dox-induced plasma protein oxidation and TNF-α release. O2-• resulted in increased oxidative damage to proteins when added to plasma and increased levels of TNF-α in macrophage culture, providing strong evidence that O2-• is responsible for these Dox-induced toxicities.

Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors into account, it’s surprising that little research has been done to elucidate the mechanisms behind aged subjects’ enhanced vulnerability to new onset psychosocial stress. Our lab embarked on a series of studies to test the effects of age and psychosocial stress on sleep architecture and cognition. Our first study measured sleep stages in young adult and aged F344 rats during their resting and active periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken. We confirmed previous studies that found impaired cognition and decreased resting deep sleep with age. However, it was increased active deep sleep that correlated best with poor cognitive performance. In the second study rats were subjected to immobilization (restraint stress) immediately preceding their final water maze task. Hippocampi were prepared for synaptic electrophysiology and trunk blood was taken for corticosterone measurement after post-stress sleep architecture data was collected. Young subjects responded to acute stress with decreased cognition, elevated CORT levels and altered sleep architecture. In contrast, stressed aged subjects were statistically indistinguishable from control aged subjects, suggesting that aged rats are less responsive to an acute psychosocial stress event. Together, these studies suggest that alleviating sleep dysregulation could therapeutically benefit cognition psychosocial stress resilience.

Thesis (Ph. D.)--University of North Texas, Aug., 2007. / Title from title page display. Includes bibliographical references.

The Self-Determination Theory (SDT) claims that autonomous motivation is a basic psychological need for all humans across cultures. When this need is met, individuals are predicted to experience well-being. However, it has been argued that autonomous motivation is not a basic need in the Chinese culture due to their philosophical background. Furthermore, commonly used instruments to measure well-being have been criticised for not measuring low arousal positive affect such as “harmony” or “peace of mind” which have been argued to more accurately target well-being for the Chinese population. The aim of this thesis is to give an overview of the psychological and cognitive neuroscientific research relating to intrinsic and extrinsic motivation, well-being and the associated cultural controversy. Additionally, a questionnaire-based study is reported which examine motivation type and well-being of 183 university students in China and in Sweden through self-reported data. The results support the SDT by showing that intrinsic motivation is correlated to well-being for both samples. Furthermore, the Swedish students experienced higher well-being compared to the Chinese students measured by the traditional “western” instruments. However, the Swedish and the Chinese students reported very similar peace of mind. This indicates that the commonly used instruments might not target well-being accurately universally. Limitations of the study and directions of future research is suggested in the discussion.

L'arithmétique est une des inventions majeures de l'humanité, mais il nous manque encore une compréhension globale de la façon dont le cerveau calcule les additions et soustractions. J'ai utilisé une nouvelle méthode comportementale basée sur un suivi de trajectoire capable de disséquer la succession des étapes de traitement impliquées dans les calculs arithmétiques. Les résultats sont compatibles avec un modèle de déplacement pas à pas sur une ligne numérique mentale, en commençant par l'opérande le plus grand et en ajoutant ou soustrayant de manière incrémentielle l'opérande le plus petit. Ensuite, j'ai analysé les signaux électrophysiologiques enregistrés à partir du cortex humain pendant que les sujets résolvaient des additions. L'activité globale dans le sillon intrapariétal augmentait au fur et à mesure que les opérandes grossissaient, prouvant son implication dans le calcul et la prise de décision. Étonnamment, les sites dans le gyrus temporal inférieur postérieur ont montré que l’activation initiale diminuait en fonction de la taille du problème, suggérant un engagement dans l'identification précoce de la difficulté de calcul. Enfin, j'ai enregistré des signaux de magnétoencéphalographie pendant que les sujets vérifiaient les additions et soustractions. En appliquant des techniques d'apprentissage automatique, j'ai étudié l'évolution temporelle des codes de représentation des opérandes et fourni une première image complète d'une cascade d'étapes de traitement en cours sous-jacentes au calcul arithmétique. Ainsi, cette dissertation fournit-elle plusieurs contributions sur la façon dont les concepts mathématiques élémentaires sont mis en œuvre dans le cerveau. / Arithmetic is one of the most important cultural inventions of humanity, however we still lack a comprehensive understanding of how the brain computes additions and subtractions. In the first study, I used a novel behavioral method based on trajectory tracking capable of dissecting the succession of processing stages involved in arithmetic computations. Results supported a model whereby single-digit arithmetic is computed by a stepwise displacement on a spatially organized mental number line, starting with the larger operand and incrementally adding or subtracting the smaller operand. In a second study, I analyzed electrophysiological signals recorded from the human cortex while subjects solved addition problems. I found that the overall activity in the intraparietal sulcus increased as the operands got larger, providing evidence for its involvement in arithmetic computation and decision-making. Surprisingly, sites within the posterior inferior temporal gyrus showed an initial burst of activity that decreased as a function of problem-size, suggesting an engagement in the early identification of the calculation difficulty. Lastly, I recorded magnetoencephalography signals while subjects verified additions and subtractions. By applying machine learning techniques, I investigated the temporal evolution of the representational codes of the operands and provided a first comprehensive picture of a cascade of unfolding processing stages underlying arithmetic calculation. Overall, this dissertation provides several contributions to our knowledge about how elementary mathematical concepts are implemented in the brain.

A oferta de cursos de Licenciatura em Computação vem sendo ampliada no Brasil. Esse curso pertencente a uma área de conhecimento recente: a Computação, agregando outras áreas como a Educação. Ele encerra dificuldades que exigem discussão acadêmica e social. Uma das dificuldades é a produção de material didático para ensino de Computação; esse material é desenvolvido pelos estudantes, mas, geralmente, sem base teórica adequada. Para contribuir com a superação dessa lacuna a pesquisa objetiva analisar a influência do estudo de Epistemologia Genética e Neurociência Cognitiva na produção didática de estudantes de Licenciatura em Computação, através da elaboração de problemas ou desafios de Linguagem de Programação, para o ensino de Computação no Ensino Fundamental. As atividades foram realizadas na disciplina Práticas Articuladoras em Computação IV do curso de Licenciatura em Computação, da Universidade de Santa Cruz do Sul – UNISC, com a participação de onze estudantes. As linguagens de programação exploradas para a produção do material didático foram FMSLogo, Scratch e Robokit. O levantamento dos dados contou com quatro etapas que compreenderam a produção didática dos estudantes através do desenvolvimento de problemas ou desafios de programação, o estudo das referidas teorias, em especial as categorias “Aprendizagem”, “Emoções e Sentimentos”, “Estímulo Emocional Competente”, “Abstração Reflexionante” e “Self”, a reelaboração da produção didática com base no estudo realizado e a análise dessa produção Os dados junto aos estudantes matriculados na disciplina foram coletados através de entrevista oral e de questionário online. A análise do material didático, desenvolvido pelos estudantes, verifica a presença textual dos três primeiros elementos de referência da prática computacional estabelecidos pelo Instituto de Tecnologia de Massachusetts – MIT: 1. Ação interativa-incremental, 2. Teste-depuração, 3.Reutilização-reformulação e 4.Abstração-modulação. A análise dos processos de abstração pseudoempírica e reflexionante permitiram entender que os resultados apontam a influência do estudo de Epistemologia Genética e Neurociência Cognitiva na produção didática dos estudantes de Licenciatura em Computação. Os problemas de programação reelaborados por nove estudantes apresentam modificações intermediárias ou muitas modificações. Conclui-se que a produção de material didático para o ensino de Computação no Ensino Fundamental pode assumir um caráter desafiador, através de descrição textual que privilegia a ação de quem resolve problemas de programação. / The offer of graduation programs in Computer Science for Teaching has been expended in Brazil. This graduation program belongs to a recent area of knowledge: Computing, adding other areas such as Education. It entails difficulties that require academic and social discussion. One of the difficulties is the production of didactic material for Computing Teaching; this material is developed by the students, but generally without adequate theoretical basis. In order to contribute to overcoming this gap, the objective research decided to analyze the influence of the study Genetic Epistemology and Cognitive Neuroscience in the didactic production of undergraduate students in Computer Science for Teaching, through the elaboration of problems or challenges of Programming Language, for the Computing Teaching in Elementary School. The Method relied on activities carried out in the subject Articulating Practices in Computing IV of the in Computer Science for Teaching course of the University of Santa Cruz do Sul – UNISC, with the participation of eleven students. The programming languages explored for the production of didactic material were FMSLogo, Scratch and ROBOKIT. The data collection had four stages that comprised the didactic production of the students through the development of problems or programming challenges, the study of these theories, in particular the categories “learning”, “emotions and feelings”, “competent emotional stimulus”, “reflective abstraction” and “self” the re-elaboration of didactic production based on the realized study and the analysis of this production The collected data from the enrolled students in the subject were collected through an interview based on the Jean Piaget Clinical Method and an online questionnaire. The analysis of the didactic material, developed by the students, verifies the textual presence of the first three elements of computational practice established by the Massachusetts Institute of Technology - MIT: 1. Interactive-incremental action, 2. Test-Depuration, 3. Reuse-reformulation and 4. Abstraction-modulation. The analysis of the processes of pseudoempirical and reflective abstraction processes allowed to understand that the results point to the influence of Genetic Epistemology and Cognitive Neuroscience study in the didactic production of Computer Science for Teaching students. Programming problems reworked by nine students present intermediate modifications or many modifications. It is concluded that the production of didactic material for the Computing teaching in the elementary school can assume a challenging character, through a textual description that privileges the action of those who solve programming problems.

A oferta de cursos de Licenciatura em Computação vem sendo ampliada no Brasil. Esse curso pertencente a uma área de conhecimento recente: a Computação, agregando outras áreas como a Educação. Ele encerra dificuldades que exigem discussão acadêmica e social. Uma das dificuldades é a produção de material didático para ensino de Computação; esse material é desenvolvido pelos estudantes, mas, geralmente, sem base teórica adequada. Para contribuir com a superação dessa lacuna a pesquisa objetiva analisar a influência do estudo de Epistemologia Genética e Neurociência Cognitiva na produção didática de estudantes de Licenciatura em Computação, através da elaboração de problemas ou desafios de Linguagem de Programação, para o ensino de Computação no Ensino Fundamental. As atividades foram realizadas na disciplina Práticas Articuladoras em Computação IV do curso de Licenciatura em Computação, da Universidade de Santa Cruz do Sul – UNISC, com a participação de onze estudantes. As linguagens de programação exploradas para a produção do material didático foram FMSLogo, Scratch e Robokit. O levantamento dos dados contou com quatro etapas que compreenderam a produção didática dos estudantes através do desenvolvimento de problemas ou desafios de programação, o estudo das referidas teorias, em especial as categorias “Aprendizagem”, “Emoções e Sentimentos”, “Estímulo Emocional Competente”, “Abstração Reflexionante” e “Self”, a reelaboração da produção didática com base no estudo realizado e a análise dessa produção Os dados junto aos estudantes matriculados na disciplina foram coletados através de entrevista oral e de questionário online. A análise do material didático, desenvolvido pelos estudantes, verifica a presença textual dos três primeiros elementos de referência da prática computacional estabelecidos pelo Instituto de Tecnologia de Massachusetts – MIT: 1. Ação interativa-incremental, 2. Teste-depuração, 3.Reutilização-reformulação e 4.Abstração-modulação. A análise dos processos de abstração pseudoempírica e reflexionante permitiram entender que os resultados apontam a influência do estudo de Epistemologia Genética e Neurociência Cognitiva na produção didática dos estudantes de Licenciatura em Computação. Os problemas de programação reelaborados por nove estudantes apresentam modificações intermediárias ou muitas modificações. Conclui-se que a produção de material didático para o ensino de Computação no Ensino Fundamental pode assumir um caráter desafiador, através de descrição textual que privilegia a ação de quem resolve problemas de programação. / The offer of graduation programs in Computer Science for Teaching has been expended in Brazil. This graduation program belongs to a recent area of knowledge: Computing, adding other areas such as Education. It entails difficulties that require academic and social discussion. One of the difficulties is the production of didactic material for Computing Teaching; this material is developed by the students, but generally without adequate theoretical basis. In order to contribute to overcoming this gap, the objective research decided to analyze the influence of the study Genetic Epistemology and Cognitive Neuroscience in the didactic production of undergraduate students in Computer Science for Teaching, through the elaboration of problems or challenges of Programming Language, for the Computing Teaching in Elementary School. The Method relied on activities carried out in the subject Articulating Practices in Computing IV of the in Computer Science for Teaching course of the University of Santa Cruz do Sul – UNISC, with the participation of eleven students. The programming languages explored for the production of didactic material were FMSLogo, Scratch and ROBOKIT. The data collection had four stages that comprised the didactic production of the students through the development of problems or programming challenges, the study of these theories, in particular the categories “learning”, “emotions and feelings”, “competent emotional stimulus”, “reflective abstraction” and “self” the re-elaboration of didactic production based on the realized study and the analysis of this production The collected data from the enrolled students in the subject were collected through an interview based on the Jean Piaget Clinical Method and an online questionnaire. The analysis of the didactic material, developed by the students, verifies the textual presence of the first three elements of computational practice established by the Massachusetts Institute of Technology - MIT: 1. Interactive-incremental action, 2. Test-Depuration, 3. Reuse-reformulation and 4. Abstraction-modulation. The analysis of the processes of pseudoempirical and reflective abstraction processes allowed to understand that the results point to the influence of Genetic Epistemology and Cognitive Neuroscience study in the didactic production of Computer Science for Teaching students. Programming problems reworked by nine students present intermediate modifications or many modifications. It is concluded that the production of didactic material for the Computing teaching in the elementary school can assume a challenging character, through a textual description that privileges the action of those who solve programming problems.

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

Doctorat en Sciences Psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

Individuals diagnosed with schizotypal personality disorder (SPD) exhibit patterns of cognitive deficits, neuromotor disturbances, and behavior problems similar to individuals with schizophrenia, and thus SPD is thought to represent one point on the continuum of schizophrenia spectrum disorders (SSDs). Deficits in behavior, cognition, and motor functioning have been implicated as childhood precursors of SSDs and appear to also vary as a function of gender and family history of psychopathology. As such, studies of youth may help in further identification of individuals at risk for SSDs. The current study examined the prospective associations between problem behaviors, neuromotor and neurocognitive functioning, as well as SSD symptoms, at baseline and 2-year follow-up in youth meeting criteria for SPD, other personality disorders, or healthy controls. The neuromotor and neurocognitive measures were able to significantly predict SSD symptoms and behavior problems above and beyond baseline predictors. Overall, the findings provide further support for the role of subcortical motor centers operating together with prefrontal cortical areas in the regulation of higher-order cognitive functioning and in producing the psychiatric features of SSDs. Significant correlations between gender, family history of schizophrenia, and history of head injury with symptoms, behavior, cognition, and motor functioning were also found and highlight the importance of examining the effects of these variables in future investigations. In sum, the current study helped in identifying factors that predict the clinical course of schizotypy and may shed light on the disturbed neural circuitry underlying SSDs.