Background and Purpose: Primary nocturnal enuresis (PNE) is a heterogeneous disorder with various underlying pathophysiological mechanisms. Results of our recent studies focused on the relationship of bladder function, sleep and brain function demonstrated a simultaneous occurrence of bladder and brain dysfunction in children with severe refractory PNE. We therefore proposed to use an animal model with altered bladder function to evaluate if abnormalities in bladder function induce functional derangement in brainstem micturition centers and/or sleep-arousal centers. / Materials and methods: In general, the study was divided in to 6 parts. Male Wistar rats (~ 1.5 months) were used for the study. / Study I: Establishment of animal model —— Male Wistar rats (200-220 g) underwent either Sham surgery or surgical reduction of bladder volume (RBV). Animals were used for further Cystometry, EEG, MRS and Cognitive function studies 4-5 weeks postoperatively. / Study II: Conventional Fill Cystometry (CFC) to evaluate bladder functional changes in response to surgical bladder volume reduction —— Twenty-four rats (RBV=12, SHAM 12) were used for the study. CFC was performed under conscious condition for evaluating the functional changes in response to surgical bladder capacity reduction. / Study III: Radiotelemetered EEG study to assess the impact of bladder dysfunction on sleep architecture and cortical arousals in rats —— Twenty-four rats (RBV=12, SHAM 12) were used for the study. Radiotelemeters were implanted in both groups 4 weeks post-operatively. The EEG biopotential and bladder pressure were monitored for 48 hours. Sleep architecture and cortical arousals were then evaluated manually. / Study IV: Evaluation of cognitive function following surgical bladder volume reduction —— Ninety eight rats (RBV=50, SHAM =48) were used for the study. / Morris Water Maze task: A circular plastic translucent pool half-filled with 26 ± 2ºC water, was used in the Morris Animals were given 9 consecutive training (2/day) sessions of Morris Water Maze (MWM) at 4 weeks postoperatively. / 8-arm Radial Maze: Food pellets were randomly placed inside each arm of the maze and the rats were allowed to explore the maze freely for 5 minutes. The rat was allowed to explore the maze for 5 minutes. Total time spent in each arm, total distance traveled in the maze was recorded. / Study V: Magnetic Resonance Spectroscopy to detect functional changes in brain in response to bladder dysfunction elicited by surgical bladder volume reduction —— Proton magnetic resonance spectroscopy was employed to examine brain metabolic changes in 24 rats (RBV=12, SHAM=12). Single voxel 1 H MRS experiments were performed using a 7 T MRI scanner. MR spectra were then processed using the jMRUI software. / Phase VI: Enzyme -linked immunosorbent assay for the assessment of associated changes in neurotransmitters —— Animals were euthanized after MRS study and brain samples were collected. Serotonin and dopamine levels were assessed in 10 mg of tissue extracts from brainstem and cortex, with ELISA kits. / Results: Study I: Bladder reduction surgery did not affect the increase in body weight post -operatively. Average body weight of the RBV and the sham groups were 340.2 ± 47.2 g and 340.5 ± 67.9 g respectively at 4 weeks post operatively. / Study II: Compared to sham group, the maximum cystometric capacity in animals with RBV was remarkably reduced at week 4 (0.78 ± 0.12 ml vs. 1.46 ± 0.22 ml, RBV vs. Sham respectively; p<0.005). Moreover, maximum detrusor pressure during voiding was significantly increased in RBV group at week 4 post operatively (32.4± 2.14 vs.23.27±1.2 5 cm H2O, RBV vs. Sham respectively). / Study III: Light non-repaid eye movement sleep occurred significantly more in RBV rats compared to sham group (61.8% vs 35%). Deep sleep and rapid eye movement sleep occurred significantly less in RBV group compared to that of sham group (30.7% vs 53.4%). / Study IV: Results showed that the RBV group used a significantly longer latency to locate the platform compared to Sham group (24.4s vs 17.19s, RBV vs. Sham respectively, p<0.001).. Moreover, significantly more animals from the RBV group could not complete the visit of the 8 arms of radial maze than that of the sham group. / Study V: Seven metabolites were detected and quantified. The results demonstrated significant changes in the lactate (Lac) metabolism in some specific regions of rat brain. At 4 weeks post - operatively, level of lactate significantly decreased in the hippocampus (43%, P<0.001) cingulate and retrosplenial cortex (29%, p<0.05) of RBV rats compared to that of sham rats. / Study VI: Results demonstrated a significant increase in Serotonin level in the brainstem of RBV rats compared to that of SHAM rats (23.726 + 0.88 ng/ml vs. 1.88 + 0.302 ng/ml). Dopamine levels decreased significantly in brainstem samples of RBV group compared to sham group (2.85 + 0.10 ng/ml vs. 6.85 + 0.84 ng/ml). / Conclusion: Surgical bladder volume reduction of bladder capacity can induce functional changes in the central nervous system. An alteration of the sleep architecture occurred in response to surgical reduction of bladder volume in rats, suggesting that there exists a potential for central consequences of bladder dysfunction. Bladder disorder chronically altered brain energy metabolism. Furthermore, bladder disorder altered the central neurotransmission in the brainstem and cortex. The finding of bladder dysfunction induced significant impairments in cognitive function in RBV rats, suggesting that the alteration in brain energy metabolism may contribute to the behavioral and attention problems, impaired learning and cognitive performance. / 研究背景： 原發性夜間遺尿症（PNE）是一種異質性疾病，涉及多種潛在的病理生理機制。我們最近的研究主要集中在膀胱功能，睡眠和腦功能的關係，結果顯示膀胱和腦功能障礙同時出現在患有嚴重難治性的PNE的兒童。因此，我們建議採用一種已改變膀胱功能的動物模型來評估膀胱功能異常會否引起腦幹排尿中心和/或睡眠 - 覺醒中心的功能紊亂 / 研究工具和方法： 研究被分成6個部分。雄性Wistar大鼠（約1.5個月）被用於研究。 / 研究I： 動物模型的建立 —— 雄性Wistar大鼠（200-220克），會先接受假手術或手術降低膀胱容量（RBV）。手術後4至5週，動物會進行進一步的膀胱測壓，腦電圖，MRS和認知功能研究。 / 研究II： 以常規填充膀胱測壓（CFC）評估減少膀胱容量手術對膀胱功能的變化 —— 二十四隻大鼠（RBV=12，對照=12）被用於研究。 CFC是用以評估在有意識的條件下，膀胱因膀胱容量減少的手術而引起的功能變化。 / 研究III： Radiotelemetered腦電圖研究，以評估在大鼠膀胱功能失調對睡眠結構和皮質覺醒的影響 —— 二十四隻大鼠（RBV=12，對照=12）被用於研究。膀胱容量減少的手術4週後，Radiotelemeters被植入在兩個組別的大鼠，並監測其腦電生物電勢和膀胱內壓48小時，然後手動評估睡眠結構和皮層覺醒。。 / 研究IV： 評估在膀胱容量減少的手術後對認知功能的影響 —— 103個大鼠（RBV=56，對照= =47）被用於研究。 / Morris水迷宮任務： 一個圓形的塑料半透明池盛載半滿的水，溫度介乎26 - ±2℃，手術4週後，該池被用在莫里斯動物進行連續9次Morris水迷宮（MWM）培訓（每天2次）。 / 八臂迷宮： 食物顆粒被隨機放置在迷宮的每個臂內，大鼠可以自由地探索迷宮5分鐘。大鼠被允許探索迷宮5分鐘。在每個手臂所用的總時間，以及在迷宮行走的總距離都會被記錄。 / 研究V： 以磁共振波譜檢測膀胱容量減少的手術所引起的膀胱功能障礙對腦功能的改變 —— 以質子磁共振波譜研究24隻大鼠腦內的代謝變化(RBV=12，對照==12）。以7 T MRI掃描儀進行磁共振波譜實驗，然後使用jMRUI軟件處理MR譜。 / 第六期： 以酶聯免疫吸附測定法評估神經遞質的相關變化 —— 動物在進行MRS研究後實施安樂死，並收集其腦樣品。從腦幹和皮層提取10毫克組織提取物，使用ELISA試劑盒，以評估羥色胺和多巴胺水平。 / 結果： 研究I： 膀胱容量減少手術並沒有影響體重增加。手術4週後，利巴韋林和對照實驗組的平均體重分別為340.2±47.2克和340.5±67.9克。 / 研究II： 相比起對照實驗組的動物，RBV組的最大膀胱容量顯著降低（0. 0.78 ± 0.12毫升對1.46±0.22毫升），排尿頻率顯著增加（2.53±0.30 對.0.53±0.05/hr）。此外，排尿時最大逼尿肌壓力亦顯著升高（32.0.8±2.19 比.20.37±1.2 5厘米水分子） / 研究III： 相比起對照實驗組的動物，光非快速動眼期睡眠顯著地較多發生於RBV大鼠身上（61.8％對35.6％），深層睡眠和快速動眼期睡眠顯著地較少發生在RBV組（32.3％對52.8％） / 研究IV： 結果表明，RBV組使用了顯著較長的時間來定位平台（24.4s vs. vs.17.19s）。而且，在RBV組，顯著地較多動物無法完成行走8臂的放射狀迷宮。 / 研究V： 進行檢測和定量七種代謝物。結果顯示乳酸（LAC）代謝在大鼠大腦的某些特定區域出現顯著變化。在手術4週後，相比起對照實驗組的動物，RBV組大鼠在海馬體（43％，P <0.001），扣帶和夾肌皮質（29％，P <0.05）的乳酸水平均顯著減少。 / 研究VI： 結果顯示RBV大鼠腦幹的血清素水平較對照實驗組的顯著增加（23.726+0.88納克/毫升與1.88±0.302ng/ml）。RBV大鼠腦幹的多巴胺水平則較對照實驗組的顯著下降（2.850.10納克/毫升與6.85+0.84毫微克/毫升）。 / 結論： 外科膀胱容量減少可誘導中樞神經系統的功能變化。以外科手術減少膀胱容量的大鼠亦引起睡眠結構改變，這顯示膀胱功能障礙對中樞有潛在影響。膀胱疾病長期改變大腦的能量代謝。此外，膀胱疾病亦改變了在腦幹和大腦皮層的中樞神經遞質傳遞。研究發現膀胱功能障礙顯著地損害RBV大鼠的認知功能，顯示改變大腦的能量代謝亦可導致行為和專注力的問題，從而損害學習和認知能力。 / Yeung, Chung Kwong. / Thesis Ph.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 199-230). / Abstracts also in Chinese. / Title from PDF title page (viewed on 14, September, 2016). / Yeung, Chung Kwong. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Pang Petti. / "August 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

There are numerous clinical and experimental accounts of retrograde and anterograde amnesia resulting from damage to the hippocampus (HPC). Several theories on the HPC hold that only certain types of recent memories should be affected by HPC damage. These theories do not accurately predict the circumstances within which memories are vulnerable to HPC damage. Here I show the HPC plays a role in the formation and storage of a wider range of memories than is posited in contemporary theories. I will demonstrate that an important factor in elciting retrograde amnesia is the number of similar learning episodes. Exposure to multiple problems in the same task context leads to retorgrade amnesia that is not observed when only one problem is learned under otherwise identical parameters. When multiple discriminations are learned, the output of the HPC blocks recall from and future use of the extra-HPC memory system. / x, 78 leaves : ill. ; 29 cm.

The thesis examines the ability of animals to construct a home base. The home base is a point in space where animals rear, groom, and circle and is a primary element in organized spatial behaviour (Eilam and Golani 1989). Once animals establish a home base, they make outward trips and stops, and after a series of trips and stops they return again to the home base. The home base behaviour of animals acts as a platform for asking questions about the cognitive organization of an environment. The thesis describes five main findings. Control and hippocampectomized animals use (1) proximal and (2) distal cues to form a home base and organize their behaviour. (3) Control and olfactory bulbectomized animals form home bases in the dark where as hippocampectomized animals are impaired suggesting self-movement but not olfactory cues play a role in home base behaviour. A final set of experiments demonstrated that control and hippocampectomized animals learn the position of (4) proximal and (5) distal cues so that in the cue's absence, animals still form a home base at that position. The demonstration that a central feature of exploratory behaviour, establishing a home base, is preserved in hippocampectomized rats in relation to proximal, distal, and conditioned visual cues - reveals that exploratory behaviour remains organized after hippocampal lesions. The inability of hippocampectomized rats to form a virtual home base in the absence of visual cues is discussed in relation to the idea that the hippocampus contributes to inertial behaviour that may be dependent upon self-movement cues. / xv, 232 leaves : ill. ; 29 cm.

CAPES, CNPq / O equilíbrio estático corporal é comandado por três sistemas sensoriais: o sistema vestibular, responsável pelas informações sobre a posição e os movimentos da cabeça; o sistema visual, que informa a posição espacial dos objetos em relação ao nosso corpo; e o sistema proprioceptivo, que controla a postura e a movimentação corporal. Estes três sistemas devem funcionar sempre em sintonia, caso contrário, o indivíduo apresentará problemas de equilíbrio. Dessa forma, é importante caracterizar as regiões corticais, bem como suas interações, envolvidas neste processo. Para isto, é necessário a utilização de técnicas de neuroimagem funcional, sendo a ressonância magnética funcional (RMf) uma das técnicas mais utilizadas neste campo nos dias de hoje. Entretanto, uma grande parte dos experimentos de RMf requer o uso de aparelhos eletrônicos para produzir estimulações somatosensoriais no corpo humano, onde a principal dificuldade é o seu ambiente hostil aos circuitos eletrônicos. A estimulação galvânica vestibular é um dos métodos mais utilizados para estimular o sistema vestibular. Esta consiste em fornecer uma corrente de baixa amplitude diretamente nas aferências vestibulares, a qual atua no disparo dos neurônios vestibulares primários atingindo principalmente as aferências otolíticas e as fibras dos canais semicirculares. O objetivo deste trabalho é analisar e avaliar as áreas cerebrais envolvidas com as estimulações visual e galvânica vestibular e suas interações, utilizando a técnica de RMf e um estimulador galvânico vestibular. Para tanto, como primeira etapa desta pesquisa, validou-se in vivo um estimulador galvânico vestibular. O estimulador elétrico não interferiu de forma significativa na qualidade das imagens de ressonância magnética e pode ser utilizado com segurança nos experimentos de RMf. Testes foram realizados para determinar um eletrodo suficientemente confortável para o voluntário durante a estimulação galvânica vestibular e que não causasse artefato nas imagens. Após estas etapas concluídas, 24 voluntários foram selecionados para realizarem três tarefas: uma puramente visual (um tabuleiro de xadrez piscante no centro da tela), uma puramente vestibular (pela aplicação da estimulação galvânica vestibular) e uma simultânea, com a apresentação em conjunto dos estímulos visual e vestibular. A estimulação puramente visual mostrou ativação dos córtices visual primário e associativo, enquanto que a estimulação puramente vestibular levou a ativação das principais áreas envolvidas com a função multimodal do sistema vestibular, como o córtex parietoinsular vestibular, o lóbulo parietal inferior, o giro temporal superior, o giro pré-central e o cerebelo. A estimulação simultânea dos sistemas visual e vestibular resultou na ativação dos giros frontal médio e inferior. Além do padrão de interação visual-vestibular inibitório recíproco ter sido mais evidente durante a condição simultânea, observou-se que as regiões frontais (córtex dorsomedial pré-frontal e giro frontal superior) estão envolvidas com o processamento da função executiva quando existem informações conflitantes dos sistemas visual e vestibular. / The static body equilibrium is controlled by three sensory systems: the vestibular system, responsible for informing the position and the movements of the head; the visual system, which informs the spatial objects position relative to the body; and the proprioceptive system, which controls posture and body movements. These three systems must always work in harmony, otherwise the individual will present balance problems. Thus, it is important to characterize the cortical regions, as well as their interactions, involved in this process. For this it is necessary to use functional neuroimaging techniques, the functional magnetic resonance imaging (fMRI) is one of the most used techniques in this field nowadays. However, a large fMRI experiments require the use of electronic devices for producing somatosensory stimulation in the human body, where the main difficulty is its hostile environment for electronic circuits. The galvanic vestibular stimulation is one of the most used methods to stimulate the vestibular system. This stimulation consist of applying a low current amplitude directly on vestibular afferents, which acts firing the primary vestibular neurons, affecting the otolithic afferents and the semicircular canals fibers. The objective of this work is to evaluate and analyze the brain areas involved with visual and galvanic vestibular stimulations and their interactions using fMRI. Therefore, as a first step of this research, a galvanic vestibular stimulator was validated in vivo. The electrical stimulator did not interfere in a significance way on magnetic resonance images quality and could be safely used in fMRI experiments. Tests were performed to select an electrode sufficiently comfortable for the volunteer during the galvanic vestibular stimulation and that do not cause artifacts in the images. After completed these steps, 24 subjects were selected to perform three tasks: a purely visual (a flashing checkerboard in the center of the screen), a purely vestibular (with application of galvanic vestibular stimulation) and a simultaneous, presenting the visual and vestibular stimuli together. The purely visual stimulation showed activation of the primary and associative visual cortices, while the purely vestibular stimulation led to activation of areas involved in multimodal function of the vestibular system, such as the parieto-insular vestibular cortex, the inferior parietal lobe, the superior temporal gyrus, the precentral gyrus and the cerebellum. The simultaneous stimulation of visual and vestibular systems resulted in activation of the middle and inferior frontal gyri. In addition to the reciprocal inhibitory visualvestibular interaction pattern had been more evident during the simultaneous condition, it was observed that frontal regions (dorsomedial prefrontal cortex and superior frontal gyrus) are involved with the executive function processing when there is conflicting information of visual and vestibular systems.

CAPES, CNPq / O equilíbrio estático corporal é comandado por três sistemas sensoriais: o sistema vestibular, responsável pelas informações sobre a posição e os movimentos da cabeça; o sistema visual, que informa a posição espacial dos objetos em relação ao nosso corpo; e o sistema proprioceptivo, que controla a postura e a movimentação corporal. Estes três sistemas devem funcionar sempre em sintonia, caso contrário, o indivíduo apresentará problemas de equilíbrio. Dessa forma, é importante caracterizar as regiões corticais, bem como suas interações, envolvidas neste processo. Para isto, é necessário a utilização de técnicas de neuroimagem funcional, sendo a ressonância magnética funcional (RMf) uma das técnicas mais utilizadas neste campo nos dias de hoje. Entretanto, uma grande parte dos experimentos de RMf requer o uso de aparelhos eletrônicos para produzir estimulações somatosensoriais no corpo humano, onde a principal dificuldade é o seu ambiente hostil aos circuitos eletrônicos. A estimulação galvânica vestibular é um dos métodos mais utilizados para estimular o sistema vestibular. Esta consiste em fornecer uma corrente de baixa amplitude diretamente nas aferências vestibulares, a qual atua no disparo dos neurônios vestibulares primários atingindo principalmente as aferências otolíticas e as fibras dos canais semicirculares. O objetivo deste trabalho é analisar e avaliar as áreas cerebrais envolvidas com as estimulações visual e galvânica vestibular e suas interações, utilizando a técnica de RMf e um estimulador galvânico vestibular. Para tanto, como primeira etapa desta pesquisa, validou-se in vivo um estimulador galvânico vestibular. O estimulador elétrico não interferiu de forma significativa na qualidade das imagens de ressonância magnética e pode ser utilizado com segurança nos experimentos de RMf. Testes foram realizados para determinar um eletrodo suficientemente confortável para o voluntário durante a estimulação galvânica vestibular e que não causasse artefato nas imagens. Após estas etapas concluídas, 24 voluntários foram selecionados para realizarem três tarefas: uma puramente visual (um tabuleiro de xadrez piscante no centro da tela), uma puramente vestibular (pela aplicação da estimulação galvânica vestibular) e uma simultânea, com a apresentação em conjunto dos estímulos visual e vestibular. A estimulação puramente visual mostrou ativação dos córtices visual primário e associativo, enquanto que a estimulação puramente vestibular levou a ativação das principais áreas envolvidas com a função multimodal do sistema vestibular, como o córtex parietoinsular vestibular, o lóbulo parietal inferior, o giro temporal superior, o giro pré-central e o cerebelo. A estimulação simultânea dos sistemas visual e vestibular resultou na ativação dos giros frontal médio e inferior. Além do padrão de interação visual-vestibular inibitório recíproco ter sido mais evidente durante a condição simultânea, observou-se que as regiões frontais (córtex dorsomedial pré-frontal e giro frontal superior) estão envolvidas com o processamento da função executiva quando existem informações conflitantes dos sistemas visual e vestibular. / The static body equilibrium is controlled by three sensory systems: the vestibular system, responsible for informing the position and the movements of the head; the visual system, which informs the spatial objects position relative to the body; and the proprioceptive system, which controls posture and body movements. These three systems must always work in harmony, otherwise the individual will present balance problems. Thus, it is important to characterize the cortical regions, as well as their interactions, involved in this process. For this it is necessary to use functional neuroimaging techniques, the functional magnetic resonance imaging (fMRI) is one of the most used techniques in this field nowadays. However, a large fMRI experiments require the use of electronic devices for producing somatosensory stimulation in the human body, where the main difficulty is its hostile environment for electronic circuits. The galvanic vestibular stimulation is one of the most used methods to stimulate the vestibular system. This stimulation consist of applying a low current amplitude directly on vestibular afferents, which acts firing the primary vestibular neurons, affecting the otolithic afferents and the semicircular canals fibers. The objective of this work is to evaluate and analyze the brain areas involved with visual and galvanic vestibular stimulations and their interactions using fMRI. Therefore, as a first step of this research, a galvanic vestibular stimulator was validated in vivo. The electrical stimulator did not interfere in a significance way on magnetic resonance images quality and could be safely used in fMRI experiments. Tests were performed to select an electrode sufficiently comfortable for the volunteer during the galvanic vestibular stimulation and that do not cause artifacts in the images. After completed these steps, 24 subjects were selected to perform three tasks: a purely visual (a flashing checkerboard in the center of the screen), a purely vestibular (with application of galvanic vestibular stimulation) and a simultaneous, presenting the visual and vestibular stimuli together. The purely visual stimulation showed activation of the primary and associative visual cortices, while the purely vestibular stimulation led to activation of areas involved in multimodal function of the vestibular system, such as the parieto-insular vestibular cortex, the inferior parietal lobe, the superior temporal gyrus, the precentral gyrus and the cerebellum. The simultaneous stimulation of visual and vestibular systems resulted in activation of the middle and inferior frontal gyri. In addition to the reciprocal inhibitory visualvestibular interaction pattern had been more evident during the simultaneous condition, it was observed that frontal regions (dorsomedial prefrontal cortex and superior frontal gyrus) are involved with the executive function processing when there is conflicting information of visual and vestibular systems.

Flow is a mental state characterised by a feeling of energised focus, complete involvement and success when fully immersed in an activity. The dimensions of and the conditions required for flow to occur have been explored in a broad spectrum of situational contexts. The close relationship between flow and peak performance sparked an interest in ways to induce flow. However, any process of flow induction requires a measure to trace the degree to which flow is in fact occurring. Self-reports of the flow experience are subjective and provide ad hoc information. Psycho-physiological measures, such as EEG, can provide objective and continuous indications of the degree to which flow is occurring. Unfortunately few studies have explored the relationships between psycho-physiological measures and flow. The present study was an attempt to determine the EEG correlates of flow under conditions of peak performance. Twenty participants were asked to perform a continuous visuomotor task 10 times. Time taken per task was used as an indicator of task performance. EEG recordings were done concurrently. Participants completed an Abbreviated Flow Questionnaire (AFQ) after each task and a Game Flow Inventory (GFI) after having finished all 10 tasks. On completion, performance times and associated flow scores were standardised where after the sample was segmented into a high flow - peak performance and a low flow - low performance level. Multi-variate analysis of variance (MANOVA) was conducted on the performance, flow and EEG data to establish that a significant difference existed between the two levels. In addition, a one-way analysis of variance between high and low flow data was conducted for all variables and main effects were established. Inter-correlations of all EEG data at both levels were then conducted across four brain sites (F3, C3, P3, O1). In high flow only, results indicated increased lobeta power in the sensorimotor cortex together with a unique EEG pattern showing beta band synchronisation between the prefrontal and sensori-motor areas and de-synchronisation between all other areas, while all other frequencies (delta, theta, alpha, lobeta, hibeta, and gamma) remained synchronised across all scalp locations. These findings supported a theoretical neuropsychological model of flow. / Psychology / D. Com. (Consulting Psychology)

Establishing appropriate animal models for the study of human memory is paramount to the development of memory disorder treatments. Damage to the hippocampus, a medial temporal lobe brain structure, has been implicated in the memory loss associated with Alzheimer’s disease and other dementias. In humans, the role of the hippocampus is largely defined; yet, its role in rodents is much less clear due to conflicting findings. To investigate these discrepancies, an extensive review of the rodent literature was conducted, with a focus on studies that used the Novel Object Recognition (NOR) paradigm for testing. The total amount of time the objects were explored during training and the delay imposed between training and testing seemed to determine hippocampal recruitment in rodents. Male C57BL/6J mice were implanted with bilateral dorsal CA1 guide cannulae to allow for the inactivation of the hippocampus at discrete time points in the task. The results suggest that the rodent hippocampus is crucial to the encoding, consolidation and retrieval of object memory. Next, it was determined that there is a delay-dependent involvement of the hippocampus in object memory, implying that other structures may be supporting the memory prior to the recruitment of hippocampus. In addition, when the context memory and object memory could be further dissociated, by altering the task design, the results imply a necessary role for the hippocampus in the object memory, irrespective of context. Also, making the task more perceptually demanding, by requiring the mice to perform a two-dimensional to three-dimensional association between stimuli, engaged the hippocampus. Then, in the traditional NOR task, long and short training exploration times were imposed to determine brain region activity for weak and strong object memory. The inactivation and immunohistochemistry findings imply weak object memory is perirhinal cortex dependent, while strong object memory is hippocampal-dependent. Taken together, the findings suggest that mice, like humans, process object memory on a continuum from weak to strong, recruiting the hippocampus conditionally for strong familiarity. Confirming this functional similarity between the rodent and human object memory systems could be beneficial for future studies investigating memory disorders. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

In this study, the brain of senescence accelerated mouse prone 8 (SAMP8) mice model was adopted to investigate PTMs state (especially methylation patterns) of core histones (H2A, H2B, H3 and H4). Seven methylated sites (H3K24, H3K27, H3K36, H3K79, H3R128, H4K20 and H2A R89) were detected by tandem matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) analysis. The methylation of H3K27 and H3K36 demonstrated a modulating relationship and methylated H3K27 might contribute to the hypermethylation state and gene repression in aged brain. Western blotting results showed that mono-methylated H4K20 decreased during SAMP8 mice aging and di-methylated H3K79 decreased in the brain of 12-month-old SAMP8 mice compared with age-matched senescence accelerated-resistant mouse (SAMR1) control. Di-methylated H3K79 could express in neuron cells of cerebral cortex and hippocampus. Whereas, the number of H3K79 methylation negative cells was higher in the cortex of 12-month old SAMP8 mice than that of age-matched control SAMR1 mice. Chromatin immunoprecipitation (ChIP) result indicated homeodomain transcription factor Pbx1 isoform 1 (Pbx1), transcription factors and transcriptional regulator proteins, such as T-box isoform 20, TetR family precursor BAZ2B and ribosomal protein, were recruited to methylated H3K79 site. Therefore, a model of methylated H3K79 on gene transcriptional regulation was proposed. Furthermore, the consequences of decreased H3K79 methylation in Neuro-2a (N2a) cells were investigated via transfection with Dot1 (disruptor of telomeric silencing) siRNA. After transfection, N2a cells displayed shorter neurite and less dendrite. Proteomic change in the N2a cells provided convincing evidence for the multi-function of decreased H3K79 methylation on transcriptional regulation, protein translation and folding, stress response and DNA breaks repair, which would contribute to brain dysfunction during neurodegenerative disease or aging. / Nowadays, many countries including China are experiencing aging populations. Aging has become the major risk factor for many diseases, such as neurodegenerative disease. The studies on the role of epigenetics in the aging process have grown tremendously in recent years. However, no systematic investigations have provided the information on histone post-translational modifications (PTMs) in aged brain and the roles of histone PTMs in brain aging are still unknown. / This study gave a new insight into the link between histone PTMs and brain aging. It could provide the experimental evidence for future studies and help us to better understand aging or neurodegenerative disease at epigenetic level. Furthermore, it could benefit for setting up the strategies for epigenetic therapy to neurodegenerative disease. / Wang, Chunmei. / Adviser: Ngai Saiming. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaf 136). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

In the aerobic cell, oxygen can be converted into a series of reactive metabolites, together called as "reactive oxygen species" (ROS). This large group include both radical and non-radical species such as superoxide anion (02"), hydroxyl radical ("0H), H202, nitric oxide (N0') and lipid hydroperoxides (LOOH). ROS are generated in very small amounts at all stages of aerobic life, and probably have a role in cellular regulation. However, their formation in excess leads to toxicity and damage to tissues. This situation, called 'oxidative stress', is responsible, atleast in part, to the pathophysioiogy of a number of disease states such as inflammation, arthritis, cancer, ageing, ischemia-reperfusion and several neurodegenerative disorders. Compared to other organs in the animal body, brain tissue is more vulnerable to oxidative stress. This is due to three major reasons; (1) brain has a high oxygen consumption (2) high content of polyunsaturated fatty acids and iron, that can promote lipid peroxidation, and (3) low levels of antioxidant enzymes such as catalase and glutathione peroxidase. The inability of neurons to regenerate also contributes to exacerbate an oxidant damage in the brain. The main objective of this investigation was to identify biochemical systems in the brain that are susceptible to ROS, on the following two issues: 1. What are the targets for the action of H2O2 and NO in the glycolytic cycle, the major route for the oxidation of glucose in brain? 2. What are the targets for the action of polyunsaturated fatty acids and their oxidative metabolites among the enzymes of phosphoinositide cycle (PI cycle), the ubiquitous signal transduction event in the brain? Using sheep brain cytosol , it was found that among the various glycolytic enzymes, only glyceraldehyde 3-phosphate dehydrogenase (GAPD) was inhibited by H2O2. The enzyme was purified to homogeneity from sheep brain and its inactivation with H202 was studied in detail. Commercial preparations of rabbit skeletal muscle GAPD was also used in this study. An unusual requirement of glutathione for the complete inactivtion of the enzyme by H2O2 was observed. The H2O2-inactivated GAPD was partially reactivated by prolonged treatment with thiol compounds. Using CD-spectral analysis, a significant change was found in the secondary structure in H2O2-treated GAPD. GAPD was inactivated by NO only in presence of high concentrations of DTT and after prolonged incubation. The N0-inactivated GAPD was partially reactivated by treatment with thiol compounds. A new activity, namely ADP-ribosylation (ADPR) emerged in the NO-treated mammalian, but not in yeast. GAPD, ADPR activity could be generated in GAPD through NO-independent treatments such as incubation with NADPH and aerobic dialysis. During NADPH treatment no loss of dehydrogenase activity occurred. Thus, it was concluded that loss of dehydrogenase activity and emergence of ADPR in NO-treated GAPD were not correlated but coincidental, and that NO treatment yielded small amounts of modified-GAPD that had ADPR activity. In the brain, onset of ischemia is characterized by a significant elevation in free fatty acid (FFA) levels, predominantly, arachidonic acid (AA). It is suggested that AA can be oxidised to its metabolites like prostaglandins and 15-hydroperoxy arachidonic acid (15-HPETE) and some of these might exert toxic effects during reperfusion. Using whole membranes or tissue slices prepared from rat brain, effects of polyunsaturated fatty acids and their oxidative metabolites on five enzymes of PI cycle namely PI synthase, PI and PIP kinases, agonist-stimulated PLC and DG kinase was studied. Hydroperoxides of linoleic- and arachidonic acids inactivated PI synthase selectively among the PI cycle enzymes. Interestingly, AA selectively stimulated DG kinase in neural membranes. Docasahexaenoic acid (DHA) a highly unsaturated fatty acid found in the brain, also stimulated DG kinase activity while saturated, mono-and di-unsaturated fatty acids were ineffective. It was concluded that AA and DHA have a role in modulating neural DG kinase. The data presented in the thesis indicate that ROS have selective targets in cells and the consequent protein modifications can be used to modulate cellular functions under normal and oxidative stress conditions.