发作性睡病日间警觉功能降低及其神经机制研究

发布时间：2018-06-12 12:31

本文选题：发作性睡病 + 静息态　；参考：《西南大学》2017年硕士论文

【摘要】：发作性睡病国内的发病率约万分之三,是一类罕见的慢性神经系统疾病。主要症状为不可抗拒的睡眠发作。目前对发作性睡病的概念界定为症状学描述,其四个典型临床表现为日间睡眠过多、猝倒(突然且短暂的肌张力丧失)、睡眠瘫痪、入睡前幻觉。根据患者是否存在猝倒症状将发作性睡病分为两个亚型----Ⅰ型伴猝倒发作性睡病和Ⅱ型不伴猝倒发作性睡病。Ⅰ型伴猝倒发作性睡病症状更为典型。由于人数极少且分布分散,中国社会大众、科研人员甚至医务工作者对发作性睡病这一疾病知之甚少。本研究应用程序、量表和PSG设备对发作性睡病的警觉性进行行为研究,进而结合功能磁共振技术手段探究其神经机制,结果如下:研究一发现发作性睡病存在日间警觉功能下降的现象。日间警觉功能的测查采用3种方式----精神运动警觉任务(PVT),艾普沃斯嗜睡量表(ESS)和基于多导睡眠监测设备的多次日间睡眠潜伏期测试(MSLT)。客观测量使用精神运动性警觉性任务(PVT)。通过对比发作性睡病与正常人的白天测的精神运动警觉任务结果,看到患者的反应时间长于正常人,即发作性睡病患者存在日间精神运动警觉性降低的现象。患者与正常人在艾普沃斯嗜睡量表上的得分显示患者显著高于正常人,即发作性睡病患者出现白天主观嗜睡的情况,这也从反面显示患者出现日间警觉性降低的主观估计。多次睡眠潜伏期测试可以看到患者在测试当天的日间均出现了正常人不会出现的满足诊断标准的睡眠潜伏期缩短、2次以上的起始REM等现象。综合三个任务可以看到发作性睡病患者存在主客观的日间警觉功能降低。另外,研究还发现发作性睡病患者精神运动警觉任务的结果可预测日间多次睡眠潜伏期测试结果。由于日间多次睡眠潜伏期测试耗时耗力,故希望能够找到对该测试具有预测作用的其他测试。首先,通过计算三个警觉任务之间的相关关系,发现精神运动警觉任务与日间多次睡眠潜伏期测试的REM潜伏期之间存在负相关(T=-0.879,p0.01)。其次,回归分析可以看到1/RT指标可以显著预测REM潜伏期(F=17.03*,△R2=0.73),即精神运动警觉任务可以预测日间多次小睡的REM潜伏期指标,解释力为0.73。研究二发现发作性睡病存在默认网络和左侧额顶控制网络的活动异常,同时,使用独立成分分析的方法,套用YEO的大尺度脑网络模板对发作性睡病和正常人的默认网络和额顶控制网络进行双样本T检验,结果发现:相对于正常人而言,发作性睡病左侧角回,左侧顶下小叶,左侧颞上回,左侧额中回,中央前回,中央后回,前扣带回,右侧小脑等区域出现活动降低,右侧额下回等区域出现活动增强。针对本研究中样本数量少的问题,对患者组与控制组进一步进行单样本T检验,结果显示控制组的取样偏差也许是双样本T检验中患者组与控制组在额下回区域的差异原因之一。而患者组在的取样偏差不是发作性睡病患者与控制组在角回和顶下小叶区域活动组间差异的原因。进一步相关分析结果显示,患者的角回活动强度与睡眠潜伏期存在显著的正相关(T=0.858,p0.05)。另外可以看到,发作性睡病患者精神运动警觉任务的1/RT值与额下回的活动呈现边缘显著状态,(T=-0.731,p=0.062)。在控制组中并未发现角回、顶下小叶和额下回区域与行为数据的相关性。回顾以往文献,我们发现对发作性睡病的结构研究(VBM,DTI等)多有报告到发作性睡病存在顶下小叶和额下回等区域的结构异常,这可以为本研究中发现的上述区域的静息态功能改变提供结构基础。同时,研究一我们发现,发作性睡病患者在精神运动警觉测试上的得分偏低,精神运动警觉测试可以直接测查被试保持持续注意和警觉的能力,患者在该任务上的表现也提示患者的持续注意能力存在问题,左侧额顶网络的活动减弱可以解释为患者持续注意维持困难的机制。本研究中发现的该类患者默认网络和左侧额顶控制网络的活动问题实验结果中默认网络的活动异常反应了发作性睡病与其他许多精神神经系统疾病一样存在大脑基线状态的问题,默认网络的活动减弱也可以为发作性睡病的常见症状----困倦和日间不可抑制的睡眠发作提供神经机制上的解释。不管是困倦还是日间睡眠发作都会导致研究一中出现的警觉性任务异常的现象。将上述三个重要的异常节点(左侧角回和顶下小叶、右侧额下回)作为感兴趣区提取这三个脑区的f ALFF值与警觉相关行为数据进行相关分析可以看到,发作性睡病患者的角回活动强度与MSLT中睡眠潜伏期存在正相关(T=0.858,p0.05)。结合发作性睡病的默认网络活动减弱的结果,我们看到发作性睡病默认网络的活动减弱程度与发作性睡病重要监测指标MSLT之间的关联。综上所述,研究一从行为层面证实发作性睡病存在警觉功能的异常,研究二利用脑影像的技术手段对发作性睡病警觉功能的异常做出了脑机制上的解释。
[Abstract]:The incidence of narcolepsy is about 3/10000 in China. It is a rare type of chronic nervous system disease. The main symptom is an irresistible sleep attack. The concept of narcolepsy is defined as symptomatic description. The four typical clinical manifestations are excessive daytime sleep, sudden and transient loss of muscle tension, and paralysis of sleep. Paroxysmal narcolepsy was divided into two subtypes based on the presence of sudden symptoms in the patient - type I with sudden onset of sleep and type II without sudden narcolepsy. Type I was more typical of the symptoms of sudden narcolepsy. Narcolepsy was rarely known. This study was used to study the alertness of narcolepsy by using a program, a scale and a PSG device, and then combined with a functional magnetic resonance technique to explore its neural mechanism. The results are as follows: a study of the decline in the daytime alertness of narcolepsy. The measurement of daytime vigilance. 3 methods were used - the psychomotor vigilance task (PVT), the apoworth sleepiness scale (ESS) and the multiple day sleep latency test (MSLT) based on the polysomnography. Objective measurement of the use of psychomotor vigilance task (PVT). By comparing the results of the mental exercise task of narcolepsy with normal people during the daytime test, The reaction time of the patient was longer than that of the normal person, that is, the patient with narcolepsy decreased in the daytime psychomotor vigilance. The score on the apoworth sleepiness scale showed that the patient was significantly higher than the normal person, that is, the subjective sleepiness of the patients with narcolepsy appeared in the daytime, which showed the patients from the reverse side. A subjective estimate of the decrease in daytime alertness. Multiple sleep latency tests showed that the patient's sleep latency that normal people did not appear on the day of the test was shortened, and the onset of REM was more than 2 times. The three tasks could see the subjective and subjective day vigilance of the patients with narcolepsy. In addition, the study also found that the results of mental exercise tasks in patients with narcolepsy could predict the results of multiple sleep latency tests in the day. Because the time consuming latency test was time-consuming and time-consuming, it was hoped to find other tests that were predictive of the test. First, three alerting tasks were calculated. It was found that there was a negative correlation between the vigilance task of psychomotor and the REM latency of the daily sleep latency test (T=-0.879, P0.01). Secondly, the regression analysis showed that the 1/RT index could significantly predict the REM latency (F=17.03*, Delta R2=0.73), that is, the vigilance task of Jing Shen movement can predict the REM potential of multiple naps in the day. The 0.73. study two found that there was a default network and the activity anomaly of the left top control network. At the same time, using the method of independent component analysis, the YEO large scale brain network template was used to carry out a double sample T test for the paroxysmal sleep and the normal person's default network and the forehead control network. Compared to normal people, the left angle gyrus of narcolepsy, left apical lobule, left superior temporal gyrus, left middle frontal gyrus, anterior central gyrus, central posterior gyrus, anterior cingulate gyrus, right cerebellum and other regions appeared to decrease, and the right frontal gyrus and other regions increased. One step single sample T test showed that the sampling deviation in the control group may be one of the reasons for the difference between the patient group and the control group in the lower frontal gyrus, while the sampling deviation in the patient group was not the cause of the difference between the episodic and the control groups in the angular and the lower lobular groups. The results showed that there was a significant positive correlation between the activity intensity of the angular gyrus and the sleep latency (T=0.858, P0.05). In addition, it was found that the 1/RT value of the mental exercise task of the narcolepsy patients and the activity of the lower frontal gyrus showed a marginal state, (T=-0.731, p=0.062). The angular gyrus, the lower lobule and the lower frontal gyrus were not found in the control group. The correlation between regional and behavioral data. Reviewing previous literature, we have found that the structural studies of narcolepsy (VBM, DTI, etc.) have reported structural abnormalities in the region of paroxysmal lobules and lower frontal gyrus in the presence of narcolepsy, which can provide a structural basis for the resting state function changes found in this study. We found that the patients with narcolepsy were on the low score in the mental exercise test, and the mental exercise test could directly examine the ability of the subjects to keep constant attention and vigilance. The patient's performance on this task also suggested that the patient's ability to continue to pay attention to the problem, the weakened activity of the left lateral frontal network could be interpreted as a patient. The activities of the default network and the left top control network in this study have been found in this study. The activity of the default network in this study shows that the activity of the paroxysmal sleeping disease has the same brain baselines as many other mental nervous system diseases, and the activity of the default network is weakened. The common symptoms of Narcolepsy - sleepiness and daytime uninhibited sleep episodes - provide a neurologic explanation. Either sleepy or daytime sleep attacks can lead to the phenomenon of abnormal alertness in the study. Three important abnormal nodes (the left angular gyrus and the inferior lobule, the right lower frontal gyrus) The correlation analysis between the f ALFF value of the three brain regions and the vigilance related behavior data can be found that there is a positive correlation between the angular gyrus intensity of narcolepsy patients and the sleep latency in MSLT (T=0.858, P0.05). The correlation between the degree of activity weakening of the network and the important monitoring index MSLT of narcolepsy. To sum up, the study confirmed the abnormality of the vigilance function of narcolepsy from the behavioral level. Study two the brain mechanism of the abnormal function of narcolepsy was explained by the technique of brain imaging.
【学位授予单位】：西南大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：B845

【参考文献】