Objective: Primarily, to determine the effect of olanzapine augmentation therapy on sleep architecture, specifically slow wave sleep (SWS), in the treatment of depression. Secondarily, to determine the effect of olanzapine augmentation therapy on illness severity and cognitive function. Finally, to examine the correlation between sleep architecture, illness severity and cognition. Methods: Prospective, double-blind, randomized, placebo-controlled study. Patients with major depressive disorder or bipolar disorder currently experiencing a major depressive episode were included. Patients were on a stable medication regime for 4 weeks prior and throughout the study. Sleep architecture was measured by overnight, ambulatory, polysomnography. Illness severity was determined using the Hamilton Depression Rating Scale (HDRS), Montgomery Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HARS). Cognitive function was examined using Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Working Memory (SWM), Spatial Span (SSP), and Reaction Time (RTI) tasks. Polysomnographs, clinical measures and cognitive test were administered at baseline, after 2-4 days of treatment and after 28-31 days of treatment. Results: Twenty-five patients participated in the study. There was no significant difference between olanzapine and placebo treated groups on age, gender, diagnosis, education level, employment or marital status and number of children. Latency to SWS, duration of SWS, sleep efficiency, total sleep time, total wake time and sleep latency significantly improved in olanzapine treated participants over placebo treated participants. Latency to and duration of rapid eye movement sleep was not significantly different between olanzapine and placebo treated participants. HDRS scores were significantly improved in olanzapine treated versus placebo treated participants. No significant difference between treatment groups was seen in MADRS, HARS, and subjective sleep quality scores. There was no significant difference between olanzapine and placebo treated participants in SWM, SSP or RTI tasks. Change in sleep architecture was not significantly correlated to clinical change or change in SWM, SSP or RTI. Clinical change was not significantly correlated to SWM or SSP. Clinical change, however, was significantly correlated to change in RTI, in the placebo treated group only. Conclusion: Olanzapine augmentation treatment improves SWS, sleep continuity and depressive symptoms. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2009-09-09 13:46:57.159

Objective: To primarily determine the effect of ziprasidone augmentation therapy on sleep architecture, specifically slow wave sleep (SWS) and rapid eye movement sleep (REM), in the treatment of bipolar depression. Secondarily, to determine the effect of ziprasidone augmentation treatment on clinical measures of subjective sleep quality and illness severity. Finally, to examine the correlation between change in sleep architecture and change in clinical measures. Methods: This was a prospective, double-blind, randomized, placebo-controlled study. 14 patients with bipolar disorder currently experiencing a major depressive episode were included. Patients were on a stable medication regime for 4 weeks prior to study enrollment and throughout the study. Sleep architecture was measured by overnight, ambulatory polysomnography. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and a visual analogue scale. Illness severity was determined using the 17 item Hamilton Depression Rating Scale (HAMD-17), the Montgomery Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAMA) and the Clinical Global Impression-Severity scale (CGI-S). Polysomnographs and clinical measures were administered at baseline, after 2-5 days and after 28-31 days of treatment. Results: There was no significant difference between ziprasidone and placebo treated groups on age, gender, diagnosis, education level, employment or marital status and number of children. Duration of SWS, latency to REM, duration of stage 2 sleep, total sleep time, onset to sleep latency, sleep efficiency and number of awakenings significantly improved in ziprasidone treated participants over placebo, whereas duration of REM sleep did not. CGI-S and HAMA scores were significantly improved with ziprasidone treatment. No significant difference between treatment groups was seen on the HAMD-17 and MADRS or in self-reported sleep quality. Change in REM sleep significantly correlated to change in subjective sleep quality in the ziprasidone group. Conclusion: Ziprasidone augmentation treatment in bipolar depression improves SWS duration, REM latency, and sleep continuity while also having a beneficial effect on overall illness severity and anxiety symptoms. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2011-08-02 17:39:05.883

No description available.

Human beings of all cultures build some form of shelter, and the global distribution of Homo sapiens depends on this basic trait. All great apes (chimpanzee, bonobo, gorilla, and orangutan) build analogous structures (called nests or beds) at least once a day throughout their adult lives, which suggests that this elementary technology was present before the hominid lines separated. This thesis investigates the variability and function of specifically wild chimpanzee shelters. I compared characteristics of chimpanzee nests, nesting trees, nest shape, and architecture in two savanna-dwelling populations on opposite sides of Africa: Fongoli, Senegal, and Issa, Tanzania. Savanna habitats are the most extreme habitats in which chimpanzees survive today, and may represent a similar environment to that in which early hominins evolved in the Plio-Pleistocene (Chapter 2). Investigating variation in nest-building within and between these two extreme habitats made it possible to tackle hypotheses of the shelter function of nests (Chapter 3).The influence of environment, specifically the role of protection from disease vectors and fluctuating temperatures, was assessed through a novel experiment in which I slept overnight in arboreal chimpanzee nests and on the bare earth (Chapter 4). To assess whether or not nests serve as an anti-predation function, I compared nesting in Issa, where predators are abundant, to Fongoli, where they are absent (Chapter 5). I provided further support for the thermoregulatory function of nests by showing that chimpanzees build more insulating nests in adverse weather conditions (Chapter 6).Nest-building is a learned behaviour, but its ontogeny is little known. I investigated social sources of variation in nest building in Fongoli to examine whether sex and age differences exist in nest building duration, nest position, shape and architecture (Chapter 7). Finally, ecosystem engineering is a consequence of animal construction, from ants to humans. I investigated use-wear traces around nests to assess niche construction of nest- building. I showed that chimpanzees repeatedly re-used these specific nest-spots within trees, which are pre-fabricated for future building through repeated pruning and shaping of these structures (Chapter 8).Nest building in great apes may be the foundation of constructivity in hominids. This thesis describes proximate functions and influences on nest-building variation in wild chimpanzees that help to model the evolution of shelter in hominids.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Doctor of Philosphy (PhD) / This thesis describes the work carried out during four treks, each over 10-11 days, from 1400m to 5000m in the Nepal Himalaya and further work performed during several two-night sojourns at the Barcroft Laboratory at 3800m on White Mountain in California, USA. Nineteen volunteers were studied during the treks in Nepal and seven volunteers were studied at White Mountain. All subjects were normal, healthy individuals who had not travelled to altitudes higher than 1000m in the previous twelve months. The aims of this research were to examine the effects on sleep, and the ventilatory patterns during sleep, of incremental increases in altitude by employing portable polysomnography to measure and record physiological signals. A further aim of this research was to examine the relationship between the ventilatory responses to hypoxia and hypercapnia, measured at sea level, and the development of periodic breathing during sleep at high altitude. In the final part of this thesis the possibility of preventing and treating Acute Mountain Sickness with non-invasive positive pressure ventilation while sleeping at high altitude was tested. Chapter 1 describes the background information on sleep, and breathing during sleep, at high altitudes. Most of these studies were performed in hypobaric chambers to simulate various high altitudes. One study measured sleep at high altitude after trekking, but there are no studies which systematically measure sleep and breathing throughout the whole trek. Breathing during sleep at high altitude and the physiological elements of the control of breathing (under normal/sea level conditions and under the hypobaric, hypoxic conditions present at high altitude) are described in this Chapter. The occurrence of Acute Mountain Sickness (AMS) in subjects who travel form near sea level to altitudes above 3000m is common but its pathophysiology not well understood. The background research into AMS and its treatment and prevention are also covered in Chapter 1. Chapter 2 describes the equipment and methods used in this research, including the polysomnographic equipment used to record sleep and breathing at sea level and the high altitude locations, the portable blood gas analyser used in Nepal and the equipment and methodology used to measure each individual’s ventilatory response to hypoxia and hypercapnia at sea level before ascent to the high altitude locations. Chapter 3 reports the findings on the changes to sleep at high altitude, with particular focus on changes in the amounts of total sleep, the duration of each sleep stage and its percentage of total sleep, and the number and causes of arousals from sleep that occurred during sleep at increasing altitudes. The lightest stage of sleep, Stage 1 non-rapid eye movement (NREM) sleep, was increased, as expected with increases in altitude, while the deeper stages of sleep (Stages 3 and 4 NREM sleep, also called slow wave sleep), were decreased. The increase in Stage 1 NREM in this research is in agreement with all previous findings. However, slow wave sleep, although decreased, was present in most of our subjects at all altitudes in Nepal; this finding is in contrast to most previous work, which has found a very marked reduction, even absence, of slow wave sleep at high altitude. Surprisingly, unlike experimental animal studies of chronic hypoxia, REM sleep was well maintained at all altitudes. Stage 2 NREM and REM sleep, total sleep time, sleep efficiency and spontaneous arousals were maintained at near sea level values. The total arousal index was increased with increasing altitude and this was due to the increasing severity of periodic breathing as altitude increased. An interesting finding of this research was that fewer than half the periodic breathing apneas and hypopneas resulted in arousal from sleep. There was a minor degree of upper airway obstruction in some subjects at sea level but this was almost resolved by 3500m. Chapter 4 reports the findings on the effects on breathing during sleep of the progressive increase of altitude, in particular the occurrence of periodic breathing. This Chapter also reports the results of changes to arterial blood gases as subjects ascended to higher altitudes. As expected, arterial blood gases were markedly altered at even the lowest altitude in Nepal (1400m) and this change became more pronounced at each new, higher altitude. Most subjects developed periodic breathing at high altitude but there was a wide variability between subjects as well as variability in the degree of periodic breathing that individual subjects developed at different altitudes. Some subjects developed periodic breathing at even the lowest altitude and this increased with increasing altitude; other subjects developed periodic breathing at one or two altitudes, while four subjects did not develop periodic breathing at any altitude. Ventilatory responses to hypoxia and hypercapnia, measured at sea level before departure to high altitude, was not significantly related to the development of periodic breathing when the group was analysed as a whole. However, when the subjects were grouped according to the steepness of their ventilatory response slopes, there was a pattern of higher amounts of periodic breathing in subjects with steeper ventilatory responses. Chapter 5 reports the findings of an experimental study carried out in the University of California, San Diego, Barcroft Laboratory on White Mountain in California. Seven subjects drove from sea level to 3800m in one day and stayed at this altitude for two nights. On one of the nights the subjects slept using a non-invasive positive pressure device via a face mask and this was found to significantly improve the sleeping oxyhemoglobin saturation. The use of the device was also found to eliminate the symptoms of Acute Mountain Sickness, as measured by the Lake Louise scoring system. This finding appears to confirm the hypothesis that lower oxygen saturation, particularly during sleep, is strongly correlated to the development of Acute Mountain Sickness and may represent a new treatment and prevention strategy for this very common high altitude disorder.

Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) is a serious sleep disordered affecting up to 24% of men and 9% of woman in the middle aged population. The current standard for the OSAHS diagnosis is Polysomnography (PSG), which refers to the continuous monitoring of multiple physiological variables over the course of a night. The main outcomes of the PSG test are the OSAHS severity measures, such as the Respiratory Disturbance Index (RDI), Arousal Index, Latencies and other information to determine the macro sleep architecture (MSA), which is defined by Wake, Rapid-eye-movement (REM) and non-REM states of sleep. The MSA results are essential for computing the diagnostic measures reported in a PSG. The existing methods of the MSA analysis require the recording of 5-7 electrophysiological signals, including the Electroencephalogram (EEG), Electroculogram (EOG), and the Electromyogram (EMG). Sleep clinicians have to depend on the manual scoring of the overnight data records using the criteria given by Rechtschaffen and Kales (R&K, 1968). The manual analysis of MSA is tedious, subjective and suffers from inter- and intra-scorer variability. Additionally, the RDI and the Apnea-Hypopnea Index (AHI) parameters although used as the primary measures of the OSAHS severity, suffers from subjectivity, low reproducibility and a poor correlation with the symptoms of OSAHS. Sleep is essentially a neuropsychological phenomenon, and the EEG remains the best technique for the functional imaging of the brain during sleep. The EEG is the direct result of the neuronal activity of the brain. However, despite the potential, the wealth of information available in the EEG signal remains virtually untapped in current OSAHS diagnosis. Although the EEG is extensively used in traditional sleep analysis, its usage is mainly limited to staging sleep, based on the four-decade old R&K criteria. This thesis addresses these issues plaguing the PSG. We develop a novel, fully-automated algorithm (Higher-order Estimated Sleep States, HESS-algorithm) for the MSA analysis, which requires only one channel of the EEG data. We also develop an objective MSA analysis technique that uses a single, one-dimensional slice of the Bispectrum of the EEG, representing a nonlinear transformation of a system function that can be considered as the EEG generator. The agreement between the human and the proposed technology was found to be in the range of 70%-87%, which are similar to those, possible between expert human scorers. The ability of the HESS algorithm to compute the MSA parameters reliably and objectively will make a dramatic impact on the diagnosis and treatment of OSAHS and other sleep diseases, such as insomnia. The proposed technology uses low-computation-load Bispectrum techniques independent of R&K Criteria (1968) making real-time automated analysis a reality. In the thesis we also propose a new index (the IHSI) to characterise the severity of sleep apnea. The new index is based on the hemispherical asymmetry of the brain and is computed from the EEG coherence analysis. We achieved a significant (p=0.0001) accuracy of up to 91% in classifying patients into apneic and non-apneic group. Our statistical analysis results show that the IHSI carries potential for providing us with a reproducible measure to assist in diagnosing of OSAHS. With the proposed methods in this thesis it may be possible to develop the technology that will not only attempt to screen the OSAHS patients but will be able to provide OSAHS diagnosis with detailed sleep architecture via home based test. These technologies will simplify the instrumentation dramatically and will make possible to extend EEG/MSA analysis to portable systems as well.

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Methadone is a long acting mu-opioid and is the most effective treatment for heroin addiction. However, opioids depress respiration and methadone maintenance treatment (MMT) patients have a higher mortality rate than the general population. Teichtahl et al conducted a pilot study and found 6 out of 10 MMT patients had central sleep apnea (CSA). But no definite conclusions were made regarding the prevalence and possible pathogenesis of CSA in the patients due to the small sample size and lack of blood toxicology data. The present project aims to confirm the preliminary results and further quantify the sleep disordered breathing (SDB) in stable MMT patients and to delineate the pathogenesis involved. (For complete abstract open document)

Doctor of Philosphy (PhD) / This thesis describes the work carried out during four treks, each over 10-11 days, from 1400m to 5000m in the Nepal Himalaya and further work performed during several two-night sojourns at the Barcroft Laboratory at 3800m on White Mountain in California, USA. Nineteen volunteers were studied during the treks in Nepal and seven volunteers were studied at White Mountain. All subjects were normal, healthy individuals who had not travelled to altitudes higher than 1000m in the previous twelve months. The aims of this research were to examine the effects on sleep, and the ventilatory patterns during sleep, of incremental increases in altitude by employing portable polysomnography to measure and record physiological signals. A further aim of this research was to examine the relationship between the ventilatory responses to hypoxia and hypercapnia, measured at sea level, and the development of periodic breathing during sleep at high altitude. In the final part of this thesis the possibility of preventing and treating Acute Mountain Sickness with non-invasive positive pressure ventilation while sleeping at high altitude was tested. Chapter 1 describes the background information on sleep, and breathing during sleep, at high altitudes. Most of these studies were performed in hypobaric chambers to simulate various high altitudes. One study measured sleep at high altitude after trekking, but there are no studies which systematically measure sleep and breathing throughout the whole trek. Breathing during sleep at high altitude and the physiological elements of the control of breathing (under normal/sea level conditions and under the hypobaric, hypoxic conditions present at high altitude) are described in this Chapter. The occurrence of Acute Mountain Sickness (AMS) in subjects who travel form near sea level to altitudes above 3000m is common but its pathophysiology not well understood. The background research into AMS and its treatment and prevention are also covered in Chapter 1. Chapter 2 describes the equipment and methods used in this research, including the polysomnographic equipment used to record sleep and breathing at sea level and the high altitude locations, the portable blood gas analyser used in Nepal and the equipment and methodology used to measure each individual’s ventilatory response to hypoxia and hypercapnia at sea level before ascent to the high altitude locations. Chapter 3 reports the findings on the changes to sleep at high altitude, with particular focus on changes in the amounts of total sleep, the duration of each sleep stage and its percentage of total sleep, and the number and causes of arousals from sleep that occurred during sleep at increasing altitudes. The lightest stage of sleep, Stage 1 non-rapid eye movement (NREM) sleep, was increased, as expected with increases in altitude, while the deeper stages of sleep (Stages 3 and 4 NREM sleep, also called slow wave sleep), were decreased. The increase in Stage 1 NREM in this research is in agreement with all previous findings. However, slow wave sleep, although decreased, was present in most of our subjects at all altitudes in Nepal; this finding is in contrast to most previous work, which has found a very marked reduction, even absence, of slow wave sleep at high altitude. Surprisingly, unlike experimental animal studies of chronic hypoxia, REM sleep was well maintained at all altitudes. Stage 2 NREM and REM sleep, total sleep time, sleep efficiency and spontaneous arousals were maintained at near sea level values. The total arousal index was increased with increasing altitude and this was due to the increasing severity of periodic breathing as altitude increased. An interesting finding of this research was that fewer than half the periodic breathing apneas and hypopneas resulted in arousal from sleep. There was a minor degree of upper airway obstruction in some subjects at sea level but this was almost resolved by 3500m. Chapter 4 reports the findings on the effects on breathing during sleep of the progressive increase of altitude, in particular the occurrence of periodic breathing. This Chapter also reports the results of changes to arterial blood gases as subjects ascended to higher altitudes. As expected, arterial blood gases were markedly altered at even the lowest altitude in Nepal (1400m) and this change became more pronounced at each new, higher altitude. Most subjects developed periodic breathing at high altitude but there was a wide variability between subjects as well as variability in the degree of periodic breathing that individual subjects developed at different altitudes. Some subjects developed periodic breathing at even the lowest altitude and this increased with increasing altitude; other subjects developed periodic breathing at one or two altitudes, while four subjects did not develop periodic breathing at any altitude. Ventilatory responses to hypoxia and hypercapnia, measured at sea level before departure to high altitude, was not significantly related to the development of periodic breathing when the group was analysed as a whole. However, when the subjects were grouped according to the steepness of their ventilatory response slopes, there was a pattern of higher amounts of periodic breathing in subjects with steeper ventilatory responses. Chapter 5 reports the findings of an experimental study carried out in the University of California, San Diego, Barcroft Laboratory on White Mountain in California. Seven subjects drove from sea level to 3800m in one day and stayed at this altitude for two nights. On one of the nights the subjects slept using a non-invasive positive pressure device via a face mask and this was found to significantly improve the sleeping oxyhemoglobin saturation. The use of the device was also found to eliminate the symptoms of Acute Mountain Sickness, as measured by the Lake Louise scoring system. This finding appears to confirm the hypothesis that lower oxygen saturation, particularly during sleep, is strongly correlated to the development of Acute Mountain Sickness and may represent a new treatment and prevention strategy for this very common high altitude disorder.