A complex system exists to monitor the body’s energy status and regulate food intake and energy expenditure to maintain a constant body weight. However, this homeostatic system is not the sole system regulating appetite. The hedonic system comprised of the mesolimbic reward pathway influences motivation to eat and acts alongside the homeostatic system to control feeding behaviours. It is often assumed that the hedonic system promotes the consumption of palatable, energy-dense foods and this can disrupt homeostatic mechanisms regulating food intake, resulting in energy overconsumption and weight gain in the long term. Yet, it is unclear to what extent the homeostatic system can defend body weight in an environment rich in palatable, energy-dense foods. I hypothesised that the homeostatic system compensates for the energy in palatable foods by reducing subsequent energy consumption, defined as homeostatic caloric compensation. I investigated homeostatic caloric compensation in a rat model of restricted palatable, high-sugar food access. Rats were schedule-fed moderate amounts of sweetened condensed milk (SCM) daily in addition to ad lib bland diet access. Both male and female rats calorically compensated for the energy consumed from moderate amounts of SCM through a robust and accurate reduction in energy consumed from bland diet, resulting in no short-term changes in body weight gain. However, homeostatic responses were limited as male rats were unable to fully calorically compensate for the scheduled-feeding of large amounts of SCM, an apparent loss of homeostatic control. It was not investigated whether female rats are also unable to fully calorically compensate for large amounts of SCM. It is possible that male rats consume these large amounts of SCM due to hedonic drive but continue to eat bland diet to acquire nutrients that are not present in SCM. To determine whether male rats defend bland diet consumption due to nutrient requirements, rats were schedule-fed large amounts of SCM enriched with protein or fibre. However, male rats did not fully calorically compensate for the energy in large amounts of SCM when enriched with protein or fibre. Overall, these findings demonstrate that the homeostatic system is able to respond to the hedonic consumption of palatable food through caloric compensatory mechanisms to defend body weight. However, it appears that the homeostatic system is unable to effectively respond to excessive hedonic palatable food consumption through caloric compensation alone. To shed light on what homeostatic mechanisms may underlie this compensatory behaviour, I used expression of the immediate early gene c-Fos to investigate neuronal activity following the scheduled-feeding of moderate amounts of SCM in male rats. c-Fos expression was increased in the ventral tegmental area of the mesolimbic reward pathway and in the lateral hypothalamus. The lateral hypothalamus has been proposed to act as an interface between homeostatic and hedonic systems. Therefore, in response to the hedonic consumption of palatable food, the homeostatic system and reward pathway may interact. Additionally, c-Fos expression was increased in satiety mediating brain regions of the homeostatic system, including the nucleus of the solitary tract and dorsomedial hypothalamus. This suggests that the homeostatic system may compensate for the energy in the palatable food by reducing subsequent food intake through inducing satiety. Furthermore, following the consumption of SCM, c-Fos expression was increased in magnocellular oxytocin neurons of the hypothalamic supraoptic and paraventricular nucleus. I demonstrated that the oxytocin system was activated by gut-brain signalling potentially involving the nucleus of the solitary tract. Therefore, the oxytocin system may be involved in homeostatic compensatory mechanisms triggered in response to the hedonic consumption of SCM, as part of a pathway mediating satiety. Moreover, I showed that c-Fos expression was also increased in the hypothalamic supramammillary nucleus (SuM) following the consumption of SCM. It has been previously shown that the SuM is involved in reward-related motivated behaviours and was recently implicated in the motivation to acquire and consume palatable food rewards. I also demonstrated that c-Fos expression in the SuM might be specific to the motivated consumption of palatable food, consistent with the SuM being involved in reward-related motivated behaviours. Furthermore, there is additional evidence from these studies that the SuM may functionally communicate with brain regions in the homeostatic and hedonic systems, including the lateral hypothalamus, dorsomedial hypothalamus and ventral tegmental area. Finally, I explored whether the gut-secreted orexigenic hormone ghrelin activates the SuM, as ghrelin may act at the SuM to influence feeding motivation. However, systemic ghrelin administration did not influence SuM c-Fos expression. As the SuM is activated following the consumption of SCM and may act as an interface between the homeostatic and hedonic systems, it is possible that the SuM could be a key component in the regulation of hedonic feeding. Using a rat model, I have shown that homeostatic compensatory mechanisms are triggered in response to the hedonic consumption of palatable, high-sugar food to regulate energy intake. This response is likely to involve homeostatic satiety mechanisms and interactions between multiple brain regions involved in the homeostatic and hedonic control of food intake. Overall, these findings shed light on how the homeostatic system responds to hedonic energy consumption and highlights specific brain regions that may be involved in hedonic feeding or homeostatic compensatory responses.

Orientadores: Fernando Jose Von Zuben, Patricia Amancio Vargas / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e de Computação / Made available in DSpace on 2018-08-11T19:08:31Z (GMT). No. of bitstreams: 1 Moioli_RenanCipriano_M.pdf: 1774485 bytes, checksum: fbe8aa9cf8be0ba5310723711c91235c (MD5) Previous issue date: 2008 / Resumo: Este trabalho tem como objetivos principais estudar, desenvolver e aplicar duas ferramentas computacionais bio-inspiradas em navegação autônoma de robôs. A primeira delas é representada pelos Sistemas Classificadores com Aprendizado, sendo que utilizou-se uma versão da proposta original, baseada em energia, e uma versão baseada em precisão. Adicionalmente, apresenta-se uma análise do processo de evolução das regras de inferência e da população final obtida. A segunda ferramenta trata de um modelo denominado sistema homeostático artificial evolutivo, composto por duas redes neurais artificiais recorrentes do tipo NSGasNets e um sistema endócrino artificial. O ajuste dos parâmetros do sistema é feito por meio de evolução, reduzindo-se a necessidade de codificação e parametrização a priori. São feitas análises de suas peculiaridades e de sua capacidade de adaptação. A motivação das duas propostas está no emprego conjunto de evolução e aprendizado, etapas consideradas fundamentais para a síntese de sistemas complexos adaptativos e modelagem computacional de processos cognitivos. Os experimentos visando validar as propostas envolvem simulação computacional em ambientes virtuais e implementações em um robô real do tipo Khepera II. / Abstract: The objectives of this work are to study, develop and apply two bio-inspired computational tools in robot autonomous navigation. The first tool is represented by Learning Classifier Systems, using the strength-based and the accuracy-based models. Additionally, the rule evolution mechanisms and the final evolved populations are analyzed. The second tool is a model called evolutionary artificial homeostatic system, composed of two NSGasNet recurrent artificial neural networks and an artificial endocrine system. The parameters adjustment is made by means of evolution, reducing the necessity of a priori coding and parametrization. Analysis of the system's peculiarities and its adaptation capability are made. The motivation of both proposals is on the concurrent use of evolution and learning, steps considered fundamental for the synthesis of complex adaptive systems and the computational modeling of cognitive processes. The experiments, which aim to validate both proposals, involve computational simulation in virtual environments and implementations on real Khepera II robots. / Mestrado / Engenharia de Computação / Mestre em Engenharia Elétrica

本研究嘗試檢視原發性失眠 (Primary insomnia) 患者在接受完認知行為治療後，其生理激發系統與恆定系統相關生理指標的改變，並探討其主、客觀睡眠改善與生理指標變化之間的關聯，藉以瞭解不同的生理系統在影響原發性失眠患者其主、客觀睡眠改善程度上可能的重要性。本研究透過醫師轉介，共18名原發性失眠患者 (男5人，女13人，平均年齡37.4歲) 接受7週6次的失眠認知行為治療，在接受治療的前後，分別進行一個晚上的多頻道睡眠記錄檢查與主、客觀睡眠評估。再進一步分析高頻率腦波Beta波 (14~35Hz) ，用來反應其中樞神經系統的激發，低頻率腦波Delta波 (0.5~2.5Hz) 則用來反應個案的恆定系統；另外，透過心跳變異率分析得出的參數，包括低頻率 (Low frequency，簡稱LF) 功率與高頻率 (High frequency，簡稱HF) 功率，以LF/HF的比率值測量其交感神經系統的活動，而HF/ (LF+HF) 則是測量副交感神經系統的活動。研究結果顯示個案的失眠問題在主觀睡眠評估指標上有顯著改善，而客觀睡眠評估指標與睡眠結構於入睡時間與入睡後清醒時間有顯著降低，其餘則無顯著改善。而各項生理系統指標，僅後半夜階段二的腦波的Delta波有顯著上升，其餘均無顯著地改善，而LF/HF的下降與失眠嚴重度的下降有顯著地關聯。因此，本研究顯示原發性失眠患者接受認知行為治療前後，其交感神經系統的下降與失眠嚴重度之改善有明顯關聯，推論失眠認知行為治療對於原發性失眠患者的交感神經活動的改善，可能是使其失眠嚴重度改善的關鍵。 / The present study evaluated the changes in beta and delta ranges of electroencephalogram (EEG) power and heart rate variability (HRV) after cognitive behavioural therapy for insomnia (CBT-I) to understand the effect of CBT-I on arousal system and homeostatic system. The study also examined the correlations between change of sleep measurement and the physiological index to clarify underlying mechanisms of sleep improved by CBT-I. Eighteen primary insomnia patients (5 males, 13 female, mean age = 37.4) participated in this study. The participants were scheduled to come to the sleep laboratory for polysomnographic (PSG) recording twice, one prior to CBT-I and one following CBT-I. A course of 6-session CBT-I was conducted during a period of seven weeks. Subjects’ changes in subjective ratings of sleep quality and quantity and sleep parameters in PSG were calculated. Spectrum analyses were conducted for their EEG and electrocardiogram (EKG). Beta EEG activity (14~35 Hz) was used to indicate the central nervos system (CNS) arousal level and Delta EEG activity (0.5~2.5 Hz) for the intensity of homeostatic system. Low frequency power (LF) and high frequency power (HF) of the R-R interval were calculated for heart rate variability (HRV). LF/HF ratio was used as a index of sympathetic nervous system activity and the HF/ (LF+HF) ratio as a index of parasympathetic nervous system activity. The results show subjective sleep quality of subjects were significantly improved after CBT-I. PSG shows shortened sleep onset latency and decreased wake time after sleep onset, but not in the other measures. For EEG spectrum and HRV parameters, only Delta EEG activity in stage2 of the second half of the night was significantly improved. In addition, the decrease of LF/HF significantly correlated with the improvement of the insomnia severity index. Thus, the results suggests that sleep improvements by CBT-I may be associated with the reduction of sympathetic arousal.