Review of Joyce Carol Oates's Night. Sleep. Death. The Stars.

Objective To compare the characteristics of sleep structure in patients with epilepsy at different times. Methods From March 2016 to December 2016, 88 patients with epilepsy in the Department of Neurology, the First Hospital of Shanxi Medical University were enrolled in this study, eighty patients with age and gender matched with epilepsy were selected as the subjects. According to the different seizures of epilepsy, epilepsy patients were divided into three groups: the night attack group (30 cases of epilepsy only at night), daytime attack group (30 cases of epilepsy only during daytime), and mixed attack group (28 cases of epilepsy patients who had seizures during the day and night), and healthy people (80 cases) as the control group. All groups were given polysomnography (PSG) in neurological electroencephalograph (EEG) room. The sleep parameters were analyzed by polysomnography, and the sleep structure of the epilepsy group and the healthy control group were compared. The sleep structure of the three groups of epilepsy patients was further compared. Results 1. Comparison of epilepsy group and healthy control group: the total sleep time was significantly shortened (P<0.05), sleep efficiency was significantly decreased (P<0.05), sleep latency, rapid eye movement sleep (REM) latency were extended (P<0.05). The percentage of total sleep time was significantly increased in non-rapid eye movement sleep (NREM) stage 1 and 2 and awake period (all P<0.05), NREM3 + 4 period, REM period accounted for the total sleep time percentage was significantly reduced (P<0.05). 2.Night attack group compared with daytime attack group: total sleep time was significantly reduced(P<0.05), sleep latency and REM latency prolonged, sleep efficiency decreased significantly, NREM1 and 2 stage and awake period significantly increased the percentage of total sleep time, NREM3 + 4 period, REM period accounted for the total sleep time percentage was significantly reduced (P<0.05). 3.Night attack group compared with mixed attack group: sleep latency and REM latency were significantly prolonged (P<0.05), NREM1 and 2 stage and awake accounted for a significant increase in the percentage of total sleep time (P<0.05), while the total sleep time was significantly reduced, sleep efficiency decreased significantly, NREM 3+ 4 period and REM period decreased the total sleep time percentage.4.Comparison of the mixed attack group and the daytime attack group: the total sleep time was significantly reduced(P<0.05), sleep efficiency decreased significantly(P<0.05), NREM1 and 2 stage and awake period increased the percentage of total sleep time(P<0.05), NREM3 + 4 and REM decreased the percentage of total sleep time(P<0.05), while the sleep latency and REM latency were significantly prolonged(P<0.05). Conclusion 1.There is a significant difference in the sleep structure between the epilepsy group and the healthy control group.2.There are significant differences in sleep structure among the three groups of night group, daytime attack group and mixed attack group, and the sleep structure of night attack group changes more. Key words: Epilepsy; Onset time; Sleep structure; Polysomnography

Sleep spindles are transient EEG oscillations of about 12-16 Hz. Together with slow waves, they hallmark the human non-REM sleep EEG. Sleep spindles originate in the thalamus and are suggested to have a sleep protective function by reducing sensory transmission to the cortex. Other evidence points to an involvement of sleep spindles in brain plasticity processes during sleep. Previous studies have shown that sleep spindles are both under homeostatic (sleep-wake dependent) and circadian (time of day-dependent) control. Furthermore, frequency-specific topographical distribution of power density within the spindle frequency range has been reported. The aim of this thesis was to assess homeostatic and circadian influences on spectral spindle frequency activity (SFA) and spindle parameters in different brain regions. Healthy young volunteers participated in both a 40-h sleep deprivation (SD) and a 40-h multiple nap paradigm. The recovery nights after the SD and the nap protocol served to assess the effect of enhanced and reduced homeostatic sleep pressure, respectively. The multiple nap paradigm revealed the modulation of sleep spindles across the circadian cycle. Two different methodological approaches were used to analyze the EEGs: classical spectral analysis (Fast Fourier Transform, FFT) and a new method for instantaneous spectral analysis (Fast Time Frequency Transform, FTFT), developed as a part of this thesis project in collaboration with Wim Martens from TEMEC, The Netherlands. Slow wave activity (SWA, spectral power density in the 0.75-4.5 Hz range) and spindle frequency activity (SFA, spectral power density in the spindle frequency range) in the high frequency range (13.75-16.5 Hz) were oppositely affected by the differential levels of sleep pressure (Chapter 2). These effects strongly depended on brain location. After SD, the SWA increase compared to the baseline night was most pronounced in the beginning of the night and in the fronto-central region. Power density in the high spindle frequency range was reduced in the centro-parietal brain region. After the nap protocol, when sleep pressure was reduced, power density in the SWA range was decreased at the beginning of the night. SFA was generally increased after the nap protocol. The data indicate that the balance between SWA and high-frequency spindle activity may represent a sensitive marker for the level of homeostatic sleep pressure. The new method of FTFT revealed that spindle density was reduced after SD (Chapter 3). This reduction was particularly apparent in the frontal derivation, and most pronounced in the first half of the night. The reduction of spindle density with its temporal and local specificity confirms the inverse homeostatic regulation of slow waves and sleep spindles. Sleep spindles had a lower frequency and a higher amplitude after SD. Within an individual spindle, frequency variability was reduced, which indicates that sleep spindles were more stable and homogenous after SD. The increase in spindle amplitude and the reduced intra-spindle frequency variability suggests a higher degree of synchronization in thalamocortical neurons under high homeostatic sleep pressure. EEGs during the nap paradigm were analyzed to compare SFA and sleep spindle characteristics during and outside the circadian phase of melatonin secretion (the “biological night” and “biological day”, respectively) (Chapter 4). In naps occurring during the phase of melatonin secretion, lower spindle frequencies were promoted, indexed as a reduction in mean spindle frequency (i.e. slowing of sleep spindles) and an increase in spindle amplitude and SFA in the low-frequency range (up to ~14.25 Hz) paralleled by a reduction in the high-frequency range (~ 14.5-16 Hz). Furthermore, spindle density was increased, and intra-spindle frequency variability reduced during the night. Thus, the circadian pacemaker is likely to promote low-frequency, high amplitude and homogenous sleep spindles during the biological night. The circadian modulation of sleep spindles may be a way by which the circadian system modulates and times sleep consolidation. This circadian modulation clearly depended on brain location such that it was maximal in the parietal and minimal in the frontal derivation. Taken together, the segregated analysis of different spindle parameters by the new high-time and high-frequency resolution spindle analysis provides new insights into sleep spindles and their regulation. Both homeostatic and circadian processes affected sleep spindles characteristics in a topography-specific manner. These statedependent local aspects provide further evidence that sleep is a dynamic phenomenon which reflects use-dependent recovery or reactivation processes.

Transient activation phases during sleep (i.e., cortical arousals, or autonomic arousals) are generally considered to fragment sleep and, as a result, negatively impact the recuperative value of sleep (Bonnet & Arand, 2003; Wesensten, Balkin, & Belenky, 1999). Transient activation phases can occur in response to external stimuli, such as transportation noise (Basner, Muller, & Elmenhorst, 2011); they also increase with aging without external stimuli and are part of the normal aging process in humans (Bonnet & Arand, 2007; Mander, Winer, & Walker, 2017). Sleep spindles–spontaneous non-rapid eye movement sleep-related brain oscillations that also decline with aging (Purcell et al., 2017)–modify external information processing and might serve as a physiological marker of sleep-related noise sensitivity (Dang-Vu, McKinney, Buxton, Solet, & Ellenbogen, 2010). Twenty-six young (19-33 years, 12 women) and 16 older (52-70 years, 8 women) healthy volunteers underwent a repeated measures six-day laboratory study. Participants spent two noise-free nights (first and last night) and four transportation noise exposure nights (three nights with road and one with railway noise exposure in an incompletely counterbalanced sequence), two with continuous and two characterized by eventful noise (average sound levels of 45 dB, maximum sound levels between 50 and 62 dB for eventful noise). During the nights, polysomnography and body movements were recorded. Subjective sleep quality was assessed every morning and subjective sleepiness was assessed twenty times during scheduled wakefulness. Sleep staging and EEG arousal scoring followed standard criteria; sleep spindle characteristics and additional arousal response events (autonomic arousals and body movements) were identified by automatic detection algorithms. In the older individuals, sleep was more fragmented under noise exposure compared to noise-free nights, while there were no effects on sleep macrostructure and all-night arousal and awakening rates in the young, which were independent of time-in-study effects. Arousal rate variation within NREM sleep cycles was best described by a u-shaped course with variations across cycles. Older participants had higher overall arousal rates than the younger individuals with differences for the first and the fourth cycle depending on the age group. During eventful noise exposure nights, overall arousal rates were increased compared to noise-free nights. Sleep spindle rates showed an age-related decline along with more noise-induced sleep alterations. Sleep structure and continuity were not differentially affected by noise exposure in individuals with a low versus a high spindle rate. For all investigated arousal response markers (cortical arousals, awakenings, autonomic arousals, and body movements), the probability of an event-related response during eventful road and railway noise exposure nights was significantly higher than spontaneous probabilities. Awakening and EEG arousal probability from single railway noise events depended on individual (e.g., age), acoustical (e.g., maximum sound pressure level and maximum slope of the sound pressure level), and situational factors (e.g., sleep stage, time of night), but was not affected by the all-night spindle rate. Overall, the data suggest small effects of transportation noise exposure on sleep macro- and microstructure and a remarkable ability of the sleeping brain to adapt to nighttime noise. Sleep spindles are trait-like transitory EEG oscillations, which may reflect stable sleep but do not necessarily protect the sleeper against external stimuli such as nighttime transportation noise. Furthermore, when evaluating the effects of aging and nighttime noise exposure on sleep fragmentation, the physiological microstructural evolution needs to be considered.

Circadian and homeostatic sleep regulation in humans : effects of age and monochromatic light

Background: A review of sleep and athletic performance (Fullagar et al. , 2015) reported that lack of sleep could have a negative impact on cognitive and physical performance. Numerous factors (i.e. jet-lag , hotels, pre-competition anxiety, early start times) can potentially disturb the sleep routine of athletes during competition (Lastella, Lovell and Sargent, 2014). Similar research has been done during a 3-day cycling race (Lastella et al. , 2014) and during a simulated cycling grand tour (Lastella et al. , 2015). Purpose: The aim of the study was to investigate whether cyclists sleep parameters would worsen during a 5-day cycling competition. We hypothesised that total sleep time and sleep efficiency would decrease over the course of the race. Methods: 5 professional male cyclists from Androni Giocattoli – Sidermec Professional Cycling Team participated in this study during Vuelta a AndalucA­a 2019. (Mean ± SD; age: 32 ± 4 years; stature: 179.8 ± 4.2 cm; body mass 67.8 ± 1.9 kg). In order to monitor quantity and quality of sleep, actigraph watches (Actiwatch Spectrum PRO, Philips Respironics, Murrysville, PA, USA) and sleep diaries were used following a method applied several times in the literature (Halson et al. , 2014; Lastella et al. , 2014, 2015; Sargent, Halson and Roach, 2014). Data were collected for 5 days (from the night before the start of the race until the morning of the last day of competition). Since the number of cyclists per team is limited by race regulations, the Bayesian Statistical Analysis framework offers an advantage over null-hypothesis significance testing as not depending on large samples (van de Schoot and Depaoli, 2014). Results: Details of the Tour stages are shown in Table 1. A summary of the data collected are presented in Table 2. Results of Bayesian analysis can be found in Table 3. Get up time decreased over the stages (Figure 1). Cyclists woke up earlier on the first day of competition than the day before the start. Get up time was earlier the last day of competition than the first day of the race. Total sleep time decreased during the race (Figure 2) compared to the night before the start, cyclists slept less the first and the last night of the Tour, and sleep efficiency decreased during the event (Figure 3). Sleep efficiency was lower during the last night of competition compared to the night before the start of the Tour. The rest of the parameters were not affected by time. Discussion: The findings of this study demonstrate that some sleep parameters decreased over time during a multi-day cycling Tour. Sleep time decreased over the course of the Tour, with cyclists sleeping more the night before the start of the event than after the first stage. Sleep efficiency decreased during the Tour, particularly, the night prior to the final stage. Conclusions: The results of this study demonstrate that the sleep of professional cyclists is affected during a 5-day cycling Tour. These data emphasise the importance for athletes and coaches of sleep hygiene routines to optimise the quality and quantity of sleep, such as setup a consistent bedtime, control room temperature, avoid caffeine consumption 4-5h before going to bed, and reduce the use of electronic equipment prior to bedtime.

Our intention with this work was to elucidate homeostatic and circadian aspects of sleep-wake regulation in women with respect to sleep phase preference during adolescence and its association with developmental stage as well as homeostatic and circadian sleep-wake regulation in major depression. The first part of this thesis covers an ambulatory study based on a cross-sectional chronotype survey among 1’187 females aged 5 to 51 years. We investigated the influence of age on sleep phase preference as well as its relationship to the onset of menarche, which served as physiological maturation marker. Our results confirm previous findings of age-dependent changes in sleep-wake behaviour as measured by chronotype changes. We found evidence for a new biological marker for the end of adolescence since our data point towards an abrupt change in the delayed sleep phase preference in women 5 years after the onset of menarche towards advancing the sleep-wake cycle. This heralds the beginning of adult-like sleep-wake behaviour in women. We found strong evidence for a circadian misalignment in adolescents as they experience a so-called social jet-lag between week and free days accounting for up to 3 hours at the nadir of the delayed sleep phase preference 5 years after menarche. This result is of particular importance since circadian misalignment of the sleep-wake timing and the circadian pacemaker may lead to impaired alertness and performance during wakefulness as well as to sleep disorders and depression. In the second part of this thesis we compared homeostatic and circadian aspects of sleep-wake regulation in young women suffering from a major depressive disorder with age-matched young healthy women and healthy older women under low and high sleep pressure under stringently controlled laboratory conditions (constant routine conditions). The study design comprised two study protocols starting with a 8-h baseline night and ending up with a 8-h recovery night. The time between these two nights (40 hours) either consisted of sustained wakefulness or 10 short sleep-wake cycles with alternating episodes of 75 min of sleep and 150 min of wakefulness. We investigated the sleep electroencephalogram (EEG; 0.75-25 Hz) during all scheduled sleep episodes and the homeostatic sleep response to enhanced and reduced sleep pressure by EEG slow-wave activity (SWA; spectral power in the 0.75-4.5 Hz range) during the recovery nights. Sleep analysis of the 10 nap episodes allowed to compare circadian modulation of the EEG spectra between the three groups as scheduled sleep episodes occurred at different circadian phase while constant low sleep pressure was controlled for. The homeostatic sleep pressure was overexpressed in young depressed women compared to both healthy control groups under high sleep pressure as well as under low sleep pressure conditions as indexed by significantly higher frontal EEG SWA during baseline and recovery nights. This result was endorsed by significantly enhanced subjective sleepiness in young depressed volunteers under low sleep pressure conditions and higher EEG SWA during the diurnal nap sleep episodes. A reduced melatonin amplitude in the depressed women compared to the healthy young volunteers was observed which implies a weaker signal output of the circadian pacemaker in depression. This evidence was substantiated by the occurrence of more EEG SWA during diurnal naps in depressed volunteers. In summary, this thesis provides several insights into circadian and homeostatic aspects of the sleep-wake cycle in women during maturation and in depression. We could establish an association between changes in circadian sleep phase preference during female adolescence and physiological maturation and gained insights in age-dependent female sleep-wake behaviour. Our findings have implications on possible actions in order to prevent social jet-lag in adolescents as such that a temporal delay in school start times should be equally dynamic as the sleep phase timing developments in adolescents. Our results on sleep-wake regulation in depression revealed higher levels of SWA in frontal brain areas together with an over-steering of the homeostatic response to alterations in sleep pressure levels together with a weakening of the circadian signal output. We could thus emphasize the misbalance of the opponent interaction between circadian and homeostatic sleep regulation in young moderately depressed women without major sleep disturbances, which may also have repercussions on the treatment of the illness in this endophenotype of depression. Therefore, selective slow-wave sleep and SWA deprivation and bright light therapy could lead to a readjustment of homeostatic and circadian sleep-wake processes and to mood improvement.

The need for sleep, the so-called sleep pressure, increases continuously during wakefulness and decreases during sleep again, in particular during intense deep sleep (Borbely, 1982). This sleep homeostatic process is mediated by the increase and degradation of adenosine in frontal brain structures (Porkka-Heiskanen, 2013). At the behavioural level, it is commonly mirrored in declines of performance under high sleep pressure (Cajochen, Blatter, & Wallach, 2004). Adenosine is degraded by adenosine deaminase (ADA) (Landolt, 2008). Due to a polymorphism (rs73598374), ADA activity differs inter-individually. Lower ADA activity in G/A- compared to G/G-allele carriers (Battistuzzi, Iudicone, Santolamazza, & Petrucci, 1981)has been associated with a trait-like higher sleep pressure level, indicated by deeper sleep and worse vigilance performance (Bachmann et al., 2012). However, the impact of sleep pressure on several sleep and waking functions depends on circadian phase (Dijk & Franken, 2005): It is potentiated during the night while counteracted during daytime by circadian wake promoting mechanisms. Also, the influence of sleep pressure on neuro-behavioral performance depends on cognitive domain (Van Dongen, Baynard, Maislin, & Dinges, 2004). Performance relying on the frontal lobes, such as executive aspects of working memory (WM), has been suggested to be particularly vulnerable to high sleep pressure (Harrison & Horne, 2000). In a multi-methodological approach we compared thus circadian variations in sleep and in a set of waking functions according to the ADA-genotype. To capture both circadian variations and their interaction with sleep pressure, we compared two 40-h conditions, in which sleep pressure was either kept low by multiple napping (low sleep pressure) or accumulated during sleep deprivation (high sleep pressure). Nap sleep electroencephalographic (EEG) activity, vigilance, WM performance and underlying blood oxygen level-dependent (BOLD) activity was assessed in regular time intervals. Vigilance and WM performance was worse during high as compared to low sleep pressure, particularly during the night. Specifically in executive aspects of WM, sleep pressure-dependent performance modulations were evident in G/A- but not in G/G-allele carriers (Reichert, Maire, Gabel, Viola, et al., 2014). WM performance of G/A-allele carriers benefited during napping in particular from rapid eye movement (REM) sleep duration (Reichert, Maire, Gabel, Hofstetter, et al., 2014). At times of high circadian wake promotion G/A-allele carriers showed a reduced sleep ability, indicating changes of circadian arousal promotion in response to lower ADA activity. Accordingly, we observed at a cerebral level during high circadian sleep promotion, that G/A-allele carriers showed more corti-cal compensatory mechanisms during WM performance to cope with high sleep pressure at night. Overall, the data suggest that the impact of sleep pressure on performance, whether state- or trait-like, is modulated by circadian mechanisms. These mechanisms contribute to a differential resistance or vulnerability to sleep deprivation according to cognitive domain. References Bachmann, V., Klaus, F., Bodenmann, S., Schafer, N., Brugger, P., Huber, S., . . . Landolt, H. P. (2012). Cerebral Cortex, 22(4), 962-970. doi: bhr173 [pii]10.1093/cercor/bhr173 Borbely, A. A. (1982). A two process model of sleep regulation. Hum Neurobiol, 1(3), 195-204. Cajochen, C., Blatter, K., & Wallach, D. (2004). Psychologica Belgica, 44(1/2), 59-80. Dijk, D. J., & Franken, P. (2005). In R. T. Kryger MH, Dement WC (Ed.), Principles and Practice of Sleep Medicine (pp. 418-435). Philadelphia: Elsevier Saunders. Harrison, Y., & Horne, J. A. (2000). J Exp Psychol Appl, 6(3), 236-249. Landolt, H. P. (2008). Biochem Pharmacol, 75(11), 2070-2079. doi: 10.1016/j.bcp.2008.02.024S0006-2952(08)00104-4 [pii] Porkka-Heiskanen, T. (2013). Curr Opin Neurobiol, 23(5), 799-805. doi: 10.1016/j.conb.2013.02.010 Reichert, C. F., Maire, M., Gabel, V., Hofstetter, M., Viola, A. U., Kolodyazhniy, V., . . . Schmidt, C. (2014). PLoS One, 9(12), e113734. doi: 10.1371/journal.pone.0113734 Reichert, C. F., Maire, M., Gabel, V., Viola, A. U., Kolodyazhniy, V., Strobel, W., . . . Schmidt, C. (2014). J Biol Rhythms, 92(2), 119-130. Van Dongen, H. P., Baynard, M. D., Maislin, G., & Dinges, D. F. (2004). Sleep, 27(3), 423-433.

Objective To understand the changing characteristics of sleep quality of acute plateau nursing staff during the period of assistance to Tibet, formulate comprehensive intervention measures, improve the support ability of nursing staff, and provide the basis for effectively completing the work of plateau assistance to Tibet. Methods From November to December 2017, 12 nurses who participated in the assistance work for Tibet in Lhasa region with an altitude of 3,650 m were selected as the emergency group, and 12 nurses from a hospital in Tibet were selected as the plateau group. Pittsburgh sleep quality index (PSQI) was used to investigate the sleep quality of the acute group before and after Tibet entry and the plateau group respectively. A sleep quality survey scale was designed to investigate the sleep quality of nursing staff in the emergency group and the plateau group at 5 different shifts on the same night after admission to Tibet. Results The scores of total sleep score, sleep quality, sleep time, sleep time, sleep efficiency and daytime dysfunction in the acute group were 3.77±1.79, 0.89±0.47, 0.78±0.36, 0.76±0.41, 0.19±0.05, 0.54±0.07, and 5.37±1.23, 1.57±0.36, 1.53±0.43, 1.21±0.38, 0.72±0.10, 0.99±0.91 respectively. The differences before and after Tibet were statistically significant (t=2.327-4.399, P <0.05).The scores of sleep time, sleep time, sleep efficiency and sleep disorder in the acute group were 1.53±0.43, 1.21±0.38, 0.72±0.19, 1.16±0.21, and 1.04±0.21, 0.86±0.32, 0.39±0.31 and 0.76±0.33 respectively. The differences between the two groups were statistically significant (t=2.441-3.547, P<0.05 or 0.01).Radical groups after Tibet plateau and nursing staff sleep quality scale scores compare, radical group day shift, middle shift, night after night under three different shifts the total score of sleep quality, respectively 11.76±0.12, 11.98±0.23, 12.43±0.52, higher than that of plateau group 11.18±0.04 11.23±0.57, 11.98±0.54, the difference between two groups was statistically significant (t=15.554, 4.227, 2.07, P<0.01 or 0.05). The sleep quality score (11.38±0.36) in the night of the rest class was lower than that of the plateau group (11.92±0.38), and the difference was statistically significant (t=-3.574, P=0.002). The score of sleep quality and sleep delay of the acute group were 1.87±0.57, 1.93±0.61, and 1.39±0.39, 1.25±0.42 respectively. The difference between the two groups was statistically significant (t=2.408, 3.181, P< 0.05 or 0.01). Conclusions It is a common sleep problem for medical and nursing personnel in Tibet who rush into the plateau. Comprehensive intervention measures should be taken in advance, scientific popularization, education and health technical guidance should be carried out in the early stage, mental health conditions should be improved, and drug prevention should be taken when necessary to help medical and nursing personnel in Tibet sleep quality. Key words: Into the plateau; Nursing staff; Quality of sleep; Intervention strategy

To summarize the experience in diagnosis and treatment of pulmonary hypertension caused by sleep hypoventilation. The clinical data of 4 patients in a family with pulmonary hypertension caused by sleep hypoventilation, full brothers and sisters, 2 (Cases 1 and 2) being treated presently and 2 (Cases 3 and 4) being deceased and traced by family medical history, were retrospectively analyzed. Three of the 4 cases (cases 1, 3, and 4) were misdiagnosed as with cor pulmonale combined with pulmonary hypertension, and one case (case 2) was misdiagnosed as with primary pulmonary hypertension. Polysomnography (PSG) revealed alveolar hypoventilation-induced long period of oxygen desaturation at sleep in Cases 1 and 2, thus confirming the diagnosis. Pulmonary function test showed that the percentage of maximum inspiratory pressure (PImax) in predicted value (51.5% and 20.9%) and the maximum expiratory pressure (PEmax) in predicted value (51.3% and 29.6%) decreased, the percentage of mouth occlusion pressure (P0.1) in predicted value (141% and 133%) compensatively increased, and the respiratory muscle strength decreased in Cases 1 and 2, which suggested that there was neuromuscular disorder in these patients. Treated by noninvasive ventilation the symptoms of these 2 patients were improved and they were discharge at last. Subsequently, they were treated by long-term night noninvasive ventilation at home, and returned to normal work and life. During the follow-up for 22 and 12 months respectively after discharge, PSG showed that the alveolar hypoventilation-induced long period oxygen desaturation at sleep had been greatly improved, and echocardiogram showed that the pulmonary pressure was greatly decreased. For the patients with unexplained pulmonary hypertension, PSG monitoring and pulmonary function tests such as PImax, PEmax, and P0.1 help determine the etiology, and long-term night noninvasive ventilation at home can improve the outcome of sleep hypoventilation-induced pulmonary hypertension.

Objective To describe the clinical spectrum, especially sleep disorder in three patients diagnosed with Morvan syndrome. Methods Three consecutive patients were identified with Morvan syndrome in the Department of Neurology, Peking Union Medical College Hospital between December 2014 and March 2016. The character in three cases has been studied from several aspects such as clinical presentation, imaging, polysomnography (PSG), cerebrospinal fluid and serum. Results Serum test showed serum contactin-associated protein 2 (CASPR2)antibodies strongly positive (+ + + ) and leucine-rich glioma inactivated protein 1 antibodies positive (+ ) in three patients. Neuropsychiatric features, neuromyotonia, neuropathic pain, dysautonomia, agrypnia excitata presented in all three patients. The agrypnia excitata was characterized by severe insomnia, excessive motor activity during the night. Agrypnia excitata was diagnosed in three patients according to their history. PSG was finished in case 2 and case 3. PSG in one patient (case 2) documented severe insomnia (sleep efficiency was 59%), lack of cyclic sleep organization with a predominance of stage 1 non-rapid eye movement sleep episodes intermixed with brief rapid eye movement, and a marked reduction of spindles and delta sleep; PSG in another patient (case 3) revealed complete absence of recognizable sleep. Sleep disorders and other symptoms resolved completely or almost completely in two patients (case 1, case 2) who received immunotherapy. Case 3 died from sudden cardiac death before immunotherapy. Conclusions Morvan syndrome usually is associated with high-titer CASPR2 antibodies in serum. Agrypnia excitata is cardinal manifestation of Morvan syndrome in association with a spectrum of neurologic presentations. Early immunotherapy could provide a favorable outcome. Key words: Morvan syndrome; Insomnia; Polysomnography; Autoimmune

Objective To investigate the association between ambulatory blood pressure rhythm and urinary albumin excretion rate (UAER) in type 2 diabetes with sleep disorder patients. Methods Three hundred and seventy three in–patients with type 2 diabetes treated from May 2012 to May 2014 in Metabolic Disease Hospital of Tianjin Medical Universitywere divided into two groups according to Pittsburgh Sleep Quality Index(PSQI): patients without sleep disorder (267) and patients with sleep disorder (106). The groups were further divided into normoalbuminuria group, microalbuminuria group and macroalbuminuria group by UAER. The changes of the average blood pressure, the circadian rhythm of blood pressure, the smoothness index of blood pressure and blood pressure variation were analyzed between the two groups and each subgroup. The regression analysis were performed between sleep disorder as well as UAER and other indicators. One–way ANOVA was used to analyze data among multiple groups. LSD-t test was used to analyze data between two groups. Results (1) The average blood pressure as well as coefficient variations of blood pressure was significant higher and the decreasing percentage of blood pressure at night and smoothness index of blood pressure was significant lower in patients with sleep disorder than those in patients without sleep disorder(t=2.9924- 5.3979, all P<0.05). (2) The average blood pressure and coefficient variation of blood pressure increased and the decreasing percentage of blood pressure at night and smoothness index of blood pressure decreased in all with and without sleep disorder subgroup patients with the increasing UAER. Significant changes of the above indicators were in sleep disorder subgroup(t=2.0073-4.0395, all P<0.05). (3) sleep disorder was positively related to 24 h systolic blood pressure, systolic blood pressure at night and UAER,whereas was negatively related to the decreasing percentage of systolic blood pressure at night(Wald= 4.192,4.590,6.019,5.910, all P<0.05).UAER was positively related to PSQI score, diastolic blood pressure at night and systolic blood pressure at night, whereas was negatively related to the decreasing percentage of systolic blood pressure at night(β=0.224, 0.251, 0.287, – 0.242, all P<0.05). Conclusion Abnormal circadian rhythm of blood pressure in type 2 diabetes patients with sleep disorder may be related to UAER. Key words: Diabetes mellitus, type 2; Sleep disorder; Ambulatory blood pressure; Circadian rhythm; Urinary albumin excretion rate

The Impact of Sleep Fragmentation on Sleep Homeostasis, Brain and Peripheral Energy Metabolism and Spatial Learning

Background: It is well known, since the pioneristic observation by Jenkins and Dallenbach (Am J Psychol 1924;35:605-12), that a period of sleep provides a specific advantage for the consolidation of newly acquired informations. Recent research about the possible enhancing effect of sleep on memory consolidation has focused on procedural memory (part of non-declarative memory system, according to Squire’s taxonomy), as it appears the memory sub-system for which the available data are more consistent. The acquisition of a procedural skill follows a typical time course, consisting in a substantial practice-dependent learning followed by a slow, off-line improvement. Sleep seems to play a critical role in promoting the process of slow learning, by consolidating memory traces and making them more stable and resistant to interferences. If sleep is critical for the consolidation of a procedural skill, then an alteration of the organization of sleep should result in a less effective consolidation, and therefore in a reduced memory performance. Such alteration can be experimentally induced, as in a deprivation protocol, or it can be naturally observed in some sleep disorders as, for example, in narcolepsy. In this research, a group of narcoleptic patients, and a group of matched healthy controls, were tested in two different procedural abilities, in order to better define the size and time course of sleep contribution to memory consolidation. Experimental Procedure: A Texture Discrimination Task (Karni & Sagi, Nature 1993;365:250-2) and a Finger Tapping Task (Walker et al., Neuron 2002;35:205-11) were administered to two indipendent samples of drug-naive patients with first-diagnosed narcolepsy with cataplexy (International Classification of Sleep Disorder 2nd ed., 2005), and two samples of matched healthy controls. In the Texture Discrimination task, subjects (n=22) had to learn to recognize a complex visual array on the screen of a personal computer, while in the Finger Tapping task (n=14) they had to press a numeric sequence on a standard keyboard, as quickly and accurately as possible. Three subsequent experimental sessions were scheduled for each partecipant, namely a training session, a first retrieval session the next day, and a second retrieval session one week later. To test for possible circadian effects on learning, half of the subjects performed the training session at 11 a.m. and half at 17 p.m. Performance at training session was taken as a measure of the practice-dependent learning, while performance of subsequent sessions were taken as a measure of the consolidation level achieved respectively after one and seven nights of sleep. Between training and first retrieval session, all participants spent a night in a sleep laboratory and underwent a polygraphic recording. Results and Discussion: In both experimental tasks, while healthy controls improved their performance after one night of undisturbed sleep, narcoleptic patients showed a non statistically significant learning. Despite this, at the second retrieval session either healthy controls and narcoleptics improved their skills. Narcoleptics improved relatively more than controls between first and second retrieval session in the texture discrimination ability, while their performance remained largely lower in the motor (FTT) ability. Sleep parameters showed a grater fragmentation in the sleep of the pathological group, and a different distribution of Stage 1 and 2 NREM sleep in the two groups, being thus consistent with the hypothesis of a lower consolidation power of sleep in narcoleptic patients. Moreover, REM density of the first part of the night of healthy subjects showed a significant correlation with the amount of improvement achieved at the first retrieval session in TDT task, supporting the hypothesis that REM sleep plays an important role in the consolidation of visuo-perceptual skills. Taken together, these results speak in favor of a slower, rather than lower consolidation of procedural skills in narcoleptic patients. Finally, an explanation of the results, based on the possible role of sleep in contrasting the interference provided by task repetition is proposed.

Objective To explore the interaction between family history of diabetes and sleep duration on prevalence of type 2 diabetes mellitus (T2DM). Methods A cohort study was conducted among permanent residents aged from 18 to 75 years in Xuzhou in May 2013. On the basis of this, a followed–up study of five years was conducted among a collection of participants without T2DM, and the interaction between family history of diabetes and sleep duration on prevalence of T2DM in followed–up participants was evaluated. Non–conditional logistic regression analysis was used to analyse the association between family history of diabetes and sleep duration on prevalence of T2DM. Results Total of 15 939 participants were involved inthe followed–up study, and after five years, finally 11 842 participants were still in the cohort. The average sleep duration of total participants was (7.2±1.1) hours per night. The accumulative rate of T2DM among the followed- up participants was 3.10%. After adjusting for the confounding factors, compared with that participants with sleep duration of 6–8 h/night, individuals with sleep duration 8 hours per night (RR=1.31,95% CI: 0.96–1.74, P>0.05). Individuals with family history of diabetes were more likely to suffer from T2DM than those without(RR=4.35,95% CI:2.01- 7.14, P 8 hours per night didn't increase significantly(RR=1.12,95% CI: 0.88 – 1.59, P>0.05) when compared with participants with sleep duration of 6- 8 hours per night without family history of diabetes. After adjusted for potential confounding factors, values of the relative excess risk of interaction (RERI),the attributable proportion(AP), and the synergy index(S) for the additive interaction betweenthe family history of diabetes and sleep duration 8 hours per night. Conclusions Additive interactions exist between family history of diabetes and sleep duration 8 hours per night at the same time. Key words: Diabetes mellitus, type 2; Family history; Sleep duration; Interaction

Sleep is important for physiological and psychological restoration; as such, athletes are encouraged to prioritise sleep following training and competition. Despite this, both team and individual sport athletes appear to achieve inadequate sleep duration and/or quality. Among other potential factors (i.e. schedule, sleep environment and psychological factors), the demands of exercise training are suggested to determine the sleep duration of athletes. However, the effect of exercise training on nocturnal sleep in athletes is not well-understood. Consequently, the aim of this thesis was to elucidate the effect of exercise training on sleep by completing four studies, which tested different training demands encountered by athletes. Chapter 3 compared the sleeping patterns of athletes and non-athletes during a competition week. Thirty athletes (from team sports and individual sports) and non-athletes were monitored for their sleep over 7d via actigraphy and the Consensus Sleep Diary. Internal training load (duration x RPE) was also attained on each day using a diary. The athlete group had a lower sleep efficiency compared to non-athletes (81.7±4.8 vs. 85.3±4.0 %, p = 0.003, ES: 0.81 [moderate effect]) as a result of a longer sleep onset latency (18 vs. 10 min, p = 0.001, ES: 0.19 [small effect]). Athletes also displayed greater intra-individual variability in sleep onset latency compared with non-athletes (13±9 vs. 7±6 min, p = 0.002, ES: 0.78 [moderate effect]). Analysis of the training load diaries revealed team sport athletes, but not individual sport athletes, had a greater daily training load compared to non-athletes (650 vs. 333 AU, p 0.05). Nocturnal heart rate variability was not different between conditions, but average heart rate increased after high intensity interval exercise (50±5 beats·min-1) compared with low intensity exercise (47±5 beats·min-1, p = 0.02, ES: 1.73 [large effect]) and no exercise (47±5 beats·min-1, p = 0.028, ES: 0.98 [moderate effect]). This suggested endurance athletes may perform high and low intensity exercise interchangeably in the early evening without disruption to nocturnal sleep. Chapter 5 investigated the effect of a single high intensity interval training session, previously shown to reduce muscle glycogen stores ( 0.05). There was a reduction in maximum voluntary contraction at post (-6.5±2.6 %, p = 0.001), 24h post (-7.2±6.5%, p = 0.027) and 48h post (-4.4±4.4 %, p = 0.039) compared to pre exercise. Perceived muscle soreness was also higher at post (2±2 AU, p = 0.026), 24h post (4±2 AU, p = 0.027) and 48h post (4±2 AU, p = 0.034) compared to pre exercise (0±1 AU). These findings suggested reduced muscle glycogen stores did not impact sleep the night after exercise, neither did increased muscle damage on the next two nights. Thus, endurance athletes may be able to attain training adaptations using the ‘train high, sleep low’ paradigm without jeopardising subsequent nocturnal sleep. Within Chapter 6, an 8-week case study of an International Taekwondo athlete was conducted to explore the effect of low energy availability on sleep leading into competition. A tailored training and nutritional intervention was designed to achieve a 9.5kg reduction in body mass so the athlete could make weight for competition in the Bantamweight category. Each week, energy availability was calculated and actigraphy was used to measure sleep. Additionally, the athletes’ hydration status was monitored via urine osmolality, whilst their body composition was assessed using dual x-ray absorptiometry and the sum of skinfolds. There was no negative effect of low energy availability on nocturnal sleep based on the average sleep during -8 weeks to -4 and -3 weeks to the pre-cut stage (-2 before competition). Sleep duration and efficiency were within recommended values during these periods (>7h and 85% respectively [National Sleep Foundation]). However, during the days leading into competition (-5d), there was a noticeable reduction in the athletes’ sleep duration, though this was likely a reflection of their internal behaviour (i.e. choosing to make bedtime later). This case study suggested low energy availability does not impact sleep duration or quality. In conclusion, the four studies resulting from this thesis have provided further understanding of the effects of exercise training on subsequent nocturnal sleep within the athlete population. Based on this research, coaches can be more aware of typical situations that alter sleep. Subsequently, this information can be utilised in the organisation of athletes training regimes.