Neste trabalho estudamos os efeitos do exercício forçado diário em esteira rolante e da exposição diária ao estresse (porque o exercício forçado envolve certo grau de estresse) durante 2 ou 8 semanas em diferentes tipos de memória em ratos Wistar machos. Os testes de memória utilizados foram: habituação da exploração em um campo aberto, reconhecimento de objetos, e memória espacial no labirinto aquático de Morris. Após estes primeiros experimentos procuramos verificar também a capacidade do exercício físico em reverter o prejuízo da memória causado pela separação maternal, procedimento que causa um déficit de memória já descrito pela literatura, utilizando, também, o teste de esquiva inibitória. O estresse diário realçou a memória de habituação, os animais aprenderam após 2 mas não após 8 semanas; houve prejuízo de memória curta (MCD) e de longa duração (MLD) na tarefa do reconhecimento em 2 semanas mas somente de MCD após 8 semanas; e não houve nenhum efeito na memória espacial após 2 ou 8 semanas. O protocolo do exercício realçou também a memória de habituação no campo aberto após 2 mas não após 8 semanas; prejudicou MCD e MLD na tarefa do reconhecimento após 2 mas não após 8 semanas; e realçou uma medida importante da aprendizagem espacial após 8 semanas (latência de escape), mas não outras medidas. Em relação ao grupo de animais que foram submetidos à separação maternal verificou-se que o exercício crônico foi capaz de reverter o déficit da MCD e MLD na esquiva inibitória e da MCD no reconhecimento de objetos, mas não teve efeitos sobre o prejuízo da MLD nesta tarefa e sobre a memória espacial testada no Labirinto Aquático de Morris. Portanto, o exercício físico crônico tem uma influência positiva sobre amemória e, adicionalmente, pode ser visto como uma ferramenta terapêutica para reverter determinados déficits de memória. / Here we studied the effects of daily forced exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress) during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests were: habituation of exploration in an open field, object recognition and spatial memory in Morris water maze. After these experiments we also tried to verify the physical exercise capacity to revert the memory deficit caused by maternal deprivation, procedure that causes a memory deficit already reported, by means of the inhibitory avoidance test. Daily footshock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM) and long-term memory (LTM) of the recognition task after 2 weeks but only STM after 8 weeks; and had no effect on the spatial task after neither 2 or 8 weeks. The exercise protocol also enhanced habituation in the open field after 2 but not 8 weeks; it hindered STM and LTM in the recognition task after 2 but not at 8 weeks; and it enhanced one important measure of spatial learning after 8 weeks (latency to escape) but not other measures. In relation of the animals that was submitted to maternal deprivation we verified that the exercise is capable to revert the deficit of STM and LTM in inhibitory avoidance test and of STM in object recognition test, but don’t have any effect on the prejudice of LTM in object recognition and in spatial memory verify using the Morris water maze test. Thus, the physical exercise had a positive influence on memory and, additionally, it can be seen like one therapeutic strategy to reverts some memory deficits.

Neste trabalho estudamos os efeitos do exercício forçado diário em esteira rolante e da exposição diária ao estresse (porque o exercício forçado envolve certo grau de estresse) durante 2 ou 8 semanas em diferentes tipos de memória em ratos Wistar machos. Os testes de memória utilizados foram: habituação da exploração em um campo aberto, reconhecimento de objetos, e memória espacial no labirinto aquático de Morris. Após estes primeiros experimentos procuramos verificar também a capacidade do exercício físico em reverter o prejuízo da memória causado pela separação maternal, procedimento que causa um déficit de memória já descrito pela literatura, utilizando, também, o teste de esquiva inibitória. O estresse diário realçou a memória de habituação, os animais aprenderam após 2 mas não após 8 semanas; houve prejuízo de memória curta (MCD) e de longa duração (MLD) na tarefa do reconhecimento em 2 semanas mas somente de MCD após 8 semanas; e não houve nenhum efeito na memória espacial após 2 ou 8 semanas. O protocolo do exercício realçou também a memória de habituação no campo aberto após 2 mas não após 8 semanas; prejudicou MCD e MLD na tarefa do reconhecimento após 2 mas não após 8 semanas; e realçou uma medida importante da aprendizagem espacial após 8 semanas (latência de escape), mas não outras medidas. Em relação ao grupo de animais que foram submetidos à separação maternal verificou-se que o exercício crônico foi capaz de reverter o déficit da MCD e MLD na esquiva inibitória e da MCD no reconhecimento de objetos, mas não teve efeitos sobre o prejuízo da MLD nesta tarefa e sobre a memória espacial testada no Labirinto Aquático de Morris. Portanto, o exercício físico crônico tem uma influência positiva sobre amemória e, adicionalmente, pode ser visto como uma ferramenta terapêutica para reverter determinados déficits de memória. / Here we studied the effects of daily forced exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress) during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests were: habituation of exploration in an open field, object recognition and spatial memory in Morris water maze. After these experiments we also tried to verify the physical exercise capacity to revert the memory deficit caused by maternal deprivation, procedure that causes a memory deficit already reported, by means of the inhibitory avoidance test. Daily footshock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM) and long-term memory (LTM) of the recognition task after 2 weeks but only STM after 8 weeks; and had no effect on the spatial task after neither 2 or 8 weeks. The exercise protocol also enhanced habituation in the open field after 2 but not 8 weeks; it hindered STM and LTM in the recognition task after 2 but not at 8 weeks; and it enhanced one important measure of spatial learning after 8 weeks (latency to escape) but not other measures. In relation of the animals that was submitted to maternal deprivation we verified that the exercise is capable to revert the deficit of STM and LTM in inhibitory avoidance test and of STM in object recognition test, but don’t have any effect on the prejudice of LTM in object recognition and in spatial memory verify using the Morris water maze test. Thus, the physical exercise had a positive influence on memory and, additionally, it can be seen like one therapeutic strategy to reverts some memory deficits.

Neste trabalho estudamos os efeitos do exercício forçado diário em esteira rolante e da exposição diária ao estresse (porque o exercício forçado envolve certo grau de estresse) durante 2 ou 8 semanas em diferentes tipos de memória em ratos Wistar machos. Os testes de memória utilizados foram: habituação da exploração em um campo aberto, reconhecimento de objetos, e memória espacial no labirinto aquático de Morris. Após estes primeiros experimentos procuramos verificar também a capacidade do exercício físico em reverter o prejuízo da memória causado pela separação maternal, procedimento que causa um déficit de memória já descrito pela literatura, utilizando, também, o teste de esquiva inibitória. O estresse diário realçou a memória de habituação, os animais aprenderam após 2 mas não após 8 semanas; houve prejuízo de memória curta (MCD) e de longa duração (MLD) na tarefa do reconhecimento em 2 semanas mas somente de MCD após 8 semanas; e não houve nenhum efeito na memória espacial após 2 ou 8 semanas. O protocolo do exercício realçou também a memória de habituação no campo aberto após 2 mas não após 8 semanas; prejudicou MCD e MLD na tarefa do reconhecimento após 2 mas não após 8 semanas; e realçou uma medida importante da aprendizagem espacial após 8 semanas (latência de escape), mas não outras medidas. Em relação ao grupo de animais que foram submetidos à separação maternal verificou-se que o exercício crônico foi capaz de reverter o déficit da MCD e MLD na esquiva inibitória e da MCD no reconhecimento de objetos, mas não teve efeitos sobre o prejuízo da MLD nesta tarefa e sobre a memória espacial testada no Labirinto Aquático de Morris. Portanto, o exercício físico crônico tem uma influência positiva sobre amemória e, adicionalmente, pode ser visto como uma ferramenta terapêutica para reverter determinados déficits de memória. / Here we studied the effects of daily forced exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress) during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests were: habituation of exploration in an open field, object recognition and spatial memory in Morris water maze. After these experiments we also tried to verify the physical exercise capacity to revert the memory deficit caused by maternal deprivation, procedure that causes a memory deficit already reported, by means of the inhibitory avoidance test. Daily footshock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM) and long-term memory (LTM) of the recognition task after 2 weeks but only STM after 8 weeks; and had no effect on the spatial task after neither 2 or 8 weeks. The exercise protocol also enhanced habituation in the open field after 2 but not 8 weeks; it hindered STM and LTM in the recognition task after 2 but not at 8 weeks; and it enhanced one important measure of spatial learning after 8 weeks (latency to escape) but not other measures. In relation of the animals that was submitted to maternal deprivation we verified that the exercise is capable to revert the deficit of STM and LTM in inhibitory avoidance test and of STM in object recognition test, but don’t have any effect on the prejudice of LTM in object recognition and in spatial memory verify using the Morris water maze test. Thus, the physical exercise had a positive influence on memory and, additionally, it can be seen like one therapeutic strategy to reverts some memory deficits.

Success For Life (SFL) is a brain research-based program for children, birth through age six. This research examined the development and implementation of SFL in 13 early childhood settings. Participants were 24 female early childhood teachers and 146 (73 male) children. Teachers included seven infant, four toddler, nine preschool and four kindergarten teachers. Children included infants(n=29), toddlers(n=27), and prek/kindergartners (n=90). A Request for Proposals was disseminated to identify possible implementation sites. After participation was confirmed, teachers attended a full day's training which included a description of brain development/function, the latest brain research, how to implement SFL and other logistics of the study. Program implementation occurred over approximately four months. A field site coordinator visited each site bimonthly to provide on-going technical assistance. This was an intervention project with a pre and post implementation design. Four instruments were used: a teacher questionnaire, a classroom environment measure, a child measure and teacher journals. Results suggested that teachers became more knowledgeable about brain development research and about how children grow and learn. Teachers were better able to make connections between brain research findings and how to apply these findings to their programs and daily activities. Likewise, the environment measure indicated that teachers were better able to arrange environments for learning. They reported that children showed significant increases in skills development and performance in the following areas: physical mastery, social relations/interactions, cognitive development, and language/communications. Additionally, teachers reported improvements in emotional expression and well-being among infants and toddlers. Toddlers and preschoolers showed significant increases in creative/ artistic expression. Finally, teachers indicated that preschoolers showed increases in initiative, use of logic/mathematics skills, and musical coordination and movement. Research findings suggest that Success For Life is able to bridge the gap between theory and practice and benefits children, teachers and programs.

A fundamental question in language research is the extent to which linguistic and cognitive systems interact. The aim of this thesis is to explore that relationship across new contexts and over the entire adult lifespan. This work centers on two branches of empirical research: the first is an investigation into the impact of later-life language learning on cognitive ageing (chapters 2-4), and the second examines the cognitive mechanisms underlying communicative perspective-taking from young adulthood into old age (chapter 5). The results of these chapters demonstrate that changes to one's linguistic environment can affect cognitive functions at any age, and similarly age-related changes to cognition can affect linguistic abilities, shedding light on the extent to which language and the brain are intricately connected over the lifespan. In the discussion (chapter 6), I consider how this work contributes new insights to the field, opening the door for future research to explore methods of improving cognitive abilities and linguistic behavior in old age.

Orientador: Gabriela Castellano / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T17:19:19Z (GMT). No. of bitstreams: 1 Pereira_FabricioRamosSilvestre_D.pdf: 32802688 bytes, checksum: 367566b29c460e1b33f48f861845217a (MD5) Previous issue date: 2013 / Resumo: O conectoma cerebral refere-se ao mapeamento dos circuitos neurais com os objetivos de 1) identificar regiões que dão suporte às atividades mentais e comportamentais, e 2) detectar alterações nesses circuitos que levam a distúrbios de ordem psiquiátrica e neurológica. Na prática, os estudos de conectoma cerebral consistem na integração de técnicas multimodais de imageamento como ressonância magnética (RM), eletroencefalograma (EEG) e magnetoencefalograma (MEG) com o intuito de estimar os tipos e os níveis de conexão entre regiões cerebrais remotas. Essa "conectividade" entre regiões cerebrais é geralmente classificada em três tipos: anatômica, funcional e efetiva. No presente trabalho, as técnicas de conectividade, usando dados de MR, foram aplicadas na comparação de grupos saudáveis e patológicos. Pela técnica de conectividade anatômica observou-se anomalias na substância branca de pacientes com mutação no gene SPG11. Essa anomalias foram detectadas através da redução da anisotropia fracional (FA) e aumento da difusividade média (MD), difusividade radial (RD) e difusividade axial (AD) em regiões subcorticais dos lobos temporal e frontal, bem como no giro do cíngulo, cuneus striatum, corpo caloso e tronco cerebral. Tais achados indicam que o dano neuronal é mais difuso do que indicava a literatura. Um segundo estudo de conectividade anatômica demonstrou que esses índices de difusividade não foram robustos para diferenciar idosos com e sem diagnóstico de depressão indicando a necessidade de avanços na formulação de novos índices com maior sensibilidade. A técnica de conectividade funcional foi empregada em três estudos. No primeiro, observou-se que pacientes com epilepsia de lobo temporal medial unilateral apresentam redução da conectividade funcional durante a execução de tarefas de memória verbal e visual. Essa redução foi predominantemente ipslateral à lesão e associada ao material-específico utilizado no teste de memória. No segundo estudo, verificou-se uma redução dos padrões de conectividade funcional hipotalâmica em sujeitos obesos e a sua parcial elevação após a cirurgia bariátrica concomitantemente à redução de indicadores bioquímicos de inflamação. No terceiro estudo, observou-se que pacientes com doença de Alzheimer apresentaram elevação dos níveis de conectividade funcional na rede saliente (Salience Network) e redução na rede de modo padrão (Default-mode network). Adicionalmente, verificou-se nos pacientes a correlação positiva da síndrome hiperativa com os níveis de conectividade funcional no cíngulo anterior e em áreas da ínsula direita. O conjunto desses resultados ilustra um possível significado clínico para futuro diagnóstico e tratamento da doença de Alzheimer. Pela técnica de conectividade efetiva observou-se que em função do envelhecimento sadio há uma mudança dos parâmetros de conectividade durante a codificação de palavras com conteúdo emocional. A influência do hipocampo sobre a amígdala ipslateral é reduzida nos sujeitos mais velhos enquanto a influência da amígdala direita sobre o hipocampo direito é elevada. Tais achados reforçam a tese da ininterrupta plasticidade etária e da dinâmica cerebral normal. Essa mesma técnica foi também empregada para demonstrar os diferentes padrões de influência entre os lobos frontal e temporal de pacientes com ELTM esquerda e sujeitos controle. Encontrou-se alteração nos padrões de conectividade efetiva dos pacientes, indicando que estes podem ser potenciais biomarcadores para a epilepsia / Abstract: Connectome refers to the neural circuitry mapping aiming to identify brain regions that support mental and behavioral functions as well as to detect circuit changes that are linked to psychiatric or neurologic disorders. In practice, connectome studies link several neuroimaging approaches such as MRI, EEG and MEG by means of the estimation of connections among remote brain regions. This "connectivity" among brain regions is usually classified as anatomic, functional or effective. In this work, the technique of connectivity, using MR data, was applied to compare healthy and pathological groups. By means of the anatomical connectivity abnormalities in the white matter of patients with SPG11 mutation were observed. These abnormalities were expressed as the reduction of the levels of fractional anisotropy (FA) and the increase in mean (MD) and radial diffusivities (RD) in sub-cortical regions of temporal and frontal lobe as well as in cingulated gyrus, cuneus, striatum, corpus callosum and brainstem. These findings suggest that neuronal damage/dysfunction is more widespread than previously recognized in this condition. Another anatomical connectivity study showed that such indices of diffusivity were not robust to statistically differentiate between old subjects with and without depression. This lacking on finding differences between both groups indicates that new indices of diffusivity have to emerge in order to provide complementary information about brain subtle microstructures. Functional connectivity was applied to three studies. In the first study, it was observed that patients with unilateral medial temporal lobe epilepsy presented lower levels of functional connectivity during visual or verbal memory tasks. Such reduction was ipsilateral to the side of the lesion and associated to the specific-material used in the memory task. In the second work, the levels of functional connectivity were reduced in hypothalamic regions of obese patients but a partial reversibility of hypothalamic dysfunction was observed after bariatric surgery. In the third, patients with Alzheimer disease presented higher values of functional connectivity in the salience network and a reduction of connectivity values in the default-mode network. Also in these patients, significant correlations between the levels of hyperactivity syndrome and the salience network were observed in the anterior cingulate cortex and right insula areas. These results indicate the potential clinical significance of resting state alterations in future diagnosis and therapy of Alzheimer disease. The effective connectivity approaches demonstrated that old and young subjects have significant differences when encoding words with emotional contents. The influence of the hippocampus on the ipsilateral amygdale was lower for older subjects whereas the influence of the right amygdale on the right hippocampus was increased for these subjects. These findings suggest that brain plasticity also happens as function of age. The same approach was used to estimate the influence from frontal to temporal lobes in patients with left MTLE compared to healthy subjects. The patterns of effective connectivity were changed in patients and may be potentially considered as biomarkers for epilepsy / Doutorado / Neurociencias / Doutor em Ciências

A combined view of the human brain and computer-generated virtual realities is motivated by recent developments in cognitive neuroscience and human-computer interaction (HCI). The emergence of new theories of human brain function, together with an increasing use of realistic human-computer interaction, give reason to believe that a better understanding of the relationship between human brains and virtual realities is both possible and valuable. The concept of “presence”, described as the subjective feeling of being in a place that feels real, can serve as a cornerstone concept in the development of such an understanding, as computer-generated presence is tightly related to how human brains work in virtual realities. In this thesis, presence is related both to theoretical discussions rooted in theories of human brain function, and to measurements of brain activity during realistic interaction. The practical implications of such results are further developed by considering potential applications. This includes the development and evaluation of a prototype application, motivated by presented principles. The theoretical conception of presence in this thesis relies on general principles of brain function, and describes presence as a general cognitive function, not specifically related to virtual realities. Virtual reality (VR) is an excellent technology for investigating and taking advantage of all aspects of presence, but a more general interpretation allows the same principles to be applied to a wide range of applications. Functional magnetic resonance imaging (fMRI) was used to study the working human brain in VR. Such data can inform and constrain further discussion about presence. Using two different experimental designs we have investigated both the effect of basic aspects of VR interaction, as well as the neural correlates of disrupted presence in a naturalistic environment. Reality-based brain-computer interaction (RBBCI) is suggested as a concept for summarizing the motivations for, and the context of, applications building on an understanding of human brains in virtual realities. The RBBCI prototype application we developed did not achieve the set goals, but much remains to be investigated and lessons from our evaluation point to possible ways forward. A developed use of methods and techniques from computer gaming is of particular interest. / Ett kombinerat perspektiv på den mänskliga hjärnan och datorgenererade virtuella verkligheter motiveras av den senaste utvecklingen inom kognitiv neurovetenskap och människa-datorinteraktion (MDI). Framväxten av nya teorier om den mänskliga hjärnan, tillsammans med en ökande användning av realistisk människa-datorinteraktion, gör det troligt att en bättre förståelse för relationen mellan mänskliga hjärnor och virtuella verkligheter är både möjlig och värdefull. Begreppet "närvaro", som i detta sammanhang beskrivs som den subjektiva känslan av att vara på en plats som känns verklig, kan fungera som en hörnsten i utvecklingen av en sådan förståelse, då datorgenererad närvaro är tätt kopplat till hur mänskliga hjärnor fungerar i virtuella verkligheter. I denna avhandling kopplas närvaro både till teoretiska diskussioner grundade i teorier om den mänskliga hjärnan, och till mätningar av hjärnans aktivitet under realistisk interaktion. De praktiska konsekvenserna av sådana resultat utvecklas vidare med en närmare titt på potentiella tillämpningar. Detta inkluderar utveckling och utvärdering av en prototypapplikation, motiverad av de presenterade principerna. Den teoretiska diskussionen av närvaro i denna avhandling bygger på allmänna principer för hjärnans funktion, och beskriver känslan av närvaro som en generell kognitiv funktion, inte specifikt relaterad till virtuella verkligheter. Virtuell verklighet (virtual reality, VR) är en utmärkt teknik för att undersöka och dra nytta av alla aspekter av närvaro, men en mer allmän tolkning gör att samma principer kan tillämpas på ett brett spektrum av applikationer. Funktionell hjärnavbildning (fMRI) användes för att studera den arbetande mänskliga hjärnan i VR. Sådant data kan informera och begränsa en vidare diskussion av närvaro. Med hjälp av två olika försöksdesigner har vi har undersökt både effekten av grundläggande aspekter av VR-interaktion, och neurala korrelat av störd närvaro i en naturalistisk miljö. Verklighets-baserad hjärna-dator interaktion (reality-based brain-computer interaction, RBBCI) föreslås som ett begrepp för att sammanfatta motiv och kontext för applikationer som bygger på en förståelse av den mänskliga hjärnan i virtuella verkligheter. Den prototypapplikation vi utvecklade uppnådde inte de uppsatta målen, men mycket återstår att utforska och lärdomar från vår utvärdering pekar på möjliga vägar framåt. En vidare användning av metoder och tekniker från dataspel är speciellt intressant.

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The physical complications of Type 1 diabetes mellitus (T1DM) have been understood as an accelerated ageing process (Morley, 2008). Do people with T1DM also experience accelerated cognitive and brain ageing? Using findings from research of the normal cognitive and brain ageing process and conceptualized in theories of the functional brain changes in cognitive ageing, a combination of cognitive testing and functional magnetic resonance imaging (fMRI) techniques were used to evaluate evidence of accelerated cognitive and brain ageing in middle-aged adults with T1DM. The first part of this thesis comprises a cognitive study of 94 adults (≥ 45 years of age) with long duration (≥ 10 years) of T1DM. Participants completed cognitive assessment and questionnaires on general mood and feelings about living with diabetes. Findings highlighted the importance of microvascular disease (specifically retinopathy) as an independent predictor of cognitive function. The incidence and predictors of mild cognitive impairment (MCI) were then explored. Results indicate a higher percentage of the group met criteria for MCI than expected based on incidence rates in the general population, providing initial evidence of accelerated cognitive ageing. Psychological factors were explored next. The relationship between the measures of well-being, diabetes health, and cognitive function highlighted the need for attention to patient's psychological well-being in diabetes care. Finally, a subgroup of 30 participants between the ages of 45 and 65 who differed on severity of retinopathy were selected to take part in an fMRI study. Blood oxygen level dependent (BOLD) activity was evaluated while participants were engaged in cognitive tasks and during rest. The findings provided evidence that the pattern of BOLD activation and functional connectivity for those with high severity of retinopathy are similar to patterns found in adults over the age of 65. In line with the theories of cognitive ageing, functional brain changes appear to maintain a level of cognitive function. Evidence of accelerated brain ageing in this primarily middle-aged group, emphasizes the importance of treatments and regimens to prevent or minimize microvascular complications.

Every individual is born with different natural competencies that can be honed by both voluntary and involuntary environmental stimuli. The response our genotype decides to make, if any, towards those stimuli, determines how well our competencies develop. Each person’s coding and variations of genes will result in unique qualities in their phenotype, or physical structure. As a result, a person has various traits that are displayed through their behavior. DNA is genetically shown to express itself through traits by up to 75%. This leaves a sort of buffer of around 25%. This region is available for us to adapt to our environmental stimuli. Your innate qualities will not reach their full potential without stimulation from the environment, in a leadership case, with education and training and therefore it can be argued that environmental exposure is necessary to fully expose the potentials and capabilities of an individual, rather than instill a new skill or develop a talent that was not existent before. Innate leadership is not a permanent state, on the contrary, it is a continuously adaptive situation demanding contextual evolutionary changes or resignation from the subject occupying the role. When the needs and demands of a society or era outweigh the relevance of the innate leaders' traits and competencies, an evolution of leadership is needed to maintain a positive relationship between all parties involved. As a result, the innate leader will begin to lose their innateness in their role and unless they evolve and adapt (because the two actions are not the same) to new contextual needs, their tenure as leader will begin to be detrimental and counter-functional. What we want to put forward is a real, universal and constructive understanding of what makes a human happy, motivated and productive and how an innate person in context is a much better solution in the short and long run, for those around them when put to a task.