The default mode network (DMN) is a highly cited neural network whose functional roles are not well understood. Until recently, event related fMRI experiments used to study the DMN could only be conducted in an open-loop format. The purpose of this study was to demonstrate the potential statistical advantages of real-time fMRI studies to conduct closed-loop experiments to directly test putative DMN functions. Using both fMRI simulations and large archival datasets, we demonstrate that open-loop designs are less statistically powerful than closed-loop experiments that can trigger stimuli at controlled levels of brain activity. When simulating event scheduling on resting state data, DMN levels were normally distributed, but the event timing proved to be ineffective in capturing the highest and lowest DMN values on average across subjects. Statistical differences in DMN levels collected by the Human Connectome Project-Aging (HCP-A) during a Go/NoGo task were also reported, along with the network's distributional effects across subjects. When examining DMN levels in 136 subjects more prone to commission errors the mean DMN levels were reported to be higher during and prior to incorrect NoGo responses. Exploring DMN levels in these same individuals reacting to a Go task also revealed differing measurement patterns when compared to all 711 subjects in the study. Additionally, the distribution of total DMN levels across all participants, as well as during a Go or NoGo trial, showed a shift in the mean towards deactivation. Furthermore, the peak at this location was greater and revealed that increased sampling occurred at the mean and under sampling at the tails. Overall, the cumulative findings in this study were successful in providing statistical arguments to support propositions for more powerful closed-loop experimentation in fMRI. / Master of Science / Activity in a neural network is observed through the use of functional MRI (fMRI) by tracking higher levels of oxygenated blood to that region when active and lower quantities when inactive. Neural networks vary in their responsibilities, thus fMRI tasks are designed to trigger a response based on the functional role of the network. This can be exemplified by studying the blood flow to default mode network (DMN), a network responsible for mind wandering, during a task that requires focus. Researchers can then correlate moments of high activity, which indicates a greater degree of mind wandering, or low activity to a correct or incorrect response to the task. Unfortunately, the timing in which a task is presented to the participant is predetermined prior to the subject entering the MRI making it difficult to capture a correct or incorrect response at the precise moment of activation or deactivation. This concept is known as open-loop and often collects data at moments of neutral activity, neither high nor low. In contrast, a closed-loop design allows a researcher to monitor the DMN's activation levels in real time and present the task at a desired time. This provides more useful data to the experimenter as all recorded responses to the task correlate with exact moments of high and low activation. This makes claims about the neural network's role statistically more powerful as there is a greater quantity of data at these moments rather than during a neutral activation state. The purpose of this thesis is to provide statistical arguments that support propositions for more powerful closed-loop experimentation in fMRI.

Introdução: o Diabetes Mellitus é uma epidemia mundial de incidência crescente e alta morbi-mortalidade. Apesar de a neuropatia diabética ser a complicação neurológica mais comum, é crescente o conhecimento de que existe um acometimento do sistema nervoso central, notadamente no que concerne às alterações cognitivas. Objetivos: investigar, por meio de duas tarefas cognitivas objetivas, simples, rápidas, de baixo custo e de fácil aplicação, diferenças entre pacientes com Diabetes Mellitus Tipo 1 (DM1) e controles quanto a medidas de atenção e impulsividade, componentes-chave das funções executivas tradicionalmente avaliados por questionários subjetivos, longos, de difícil reprodutibilidade e que exigem psicólogos treinados; correlacionar as diferenças encontradas com características clínicas; explorar as correlações entre as duas tarefas. Métodos: Foram comparados os desempenhos de 20 pacientes com DM1 e 20 controles, de ambos os sexos, com idades entre 12 e 15 anos, utilizando a tarefa Agir-Não Agir e uma tarefa de Labirintos, e verificadas correlações entre eles. Resultados: o grupo DM1 teve mais respostas antecipatórias (RA) na tarefa Agir-Não Agir (p<0,05) e fez mais mudanças de trajetória nos Labirintos (p <0,01). Houve correlação entre hipoglicemias não-graves e RA (p=0,01), e entre hipoglicemias graves e número de toques nas paredes dos labirintos (p <0,05). HbA1c> 9% correlacionou-se com um maior número de becos sem saída nos labirintos (p <0,05). Os parâmetros mostraram-se coerentes dentro de cada tarefa e entre elas. Conclusões: Encontramos indicadores de desatenção e impulsividade coexistindo no DM1, o primeiro estando mais relacionado à hiperglicemia, e o último à hipoglicemia. Investigações adicionais são necessárias para estudar o declínio cognitivo associado ao diabetes por meio de avaliações mais objetivas, e avaliar a confiabilidade e as propriedades psicométricas das tarefas aqui propostas. / Background : Diabetes Mellitus is a worldwide epidemic of increasing incidence and high morbidity and mortality. Although diabetic neuropathy is the most common neurological complication, the knowledge that there is an involvement of the central nervous system is increasing, especially in relation to cognitive changes. Aims: To investigate with two simple, inexpensive, rapid, objective and easy-to-apply tasks, differences between patients with Type 1 Diabetes Mellitus (T1DM) and controls in outcome measures of attention and impulsivity, key-executive function components traditionally assessed by subjective and long questionnaires of difficult reproducibility that require trained psychologists; to correlate the alterations with clinical characteristics; to explore correlations between the tasks. Methods: We compared the scores of 20 T1DM to 20 controls, both sexes, aged 12 to 15 years, using a Go-NoGo and a Maze task, and verified correlations between them. Results: T1DM group had more anticipatory answers (AA) in Go-NoGo task (p<0,05) and made more direction changes in Mazes (p<0,01). There was correlation between non-severe hypoglycaemias and AA (p=0,01), and between severe hypoglycaemias and number of touches in Mazes’ walls (p<0,05). HbA1c>9% correlated to a greater number of alleys in Mazes (p<0,05). The tasks’ parameters were coherent among each task and between them. Conclusions: We found indicators of inattention and impulsivity coexisting in T1DM, the first more related to hyperglycaemia and the later to hypoglycemia. Further research is needed to study diabetes-associated cognitive decline with more objective parameters and evaluate the reliability and psychometric properties of the tasks herein proposed. / Dissertação (Mestrado)