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小儿睡眠呼吸暂停:夜间脑电图作为一种表型生物标志物

Pediatric Sleep Apnea: The Overnight Electroencephalogram as a Phenotypic Biomarker.

作者信息

Gutiérrez-Tobal Gonzalo C, Gomez-Pilar Javier, Kheirandish-Gozal Leila, Martín-Montero Adrián, Poza Jesús, Álvarez Daniel, Del Campo Félix, Gozal David, Hornero Roberto

机构信息

Biomedical Engineering Group, University of Valladolid, Valladolid, Spain.

Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Valladolid, Spain.

出版信息

Front Neurosci. 2021 Nov 3;15:644697. doi: 10.3389/fnins.2021.644697. eCollection 2021.

Abstract

Pediatric obstructive sleep apnea (OSA) is a prevalent disorder that disrupts sleep and is associated with neurocognitive and behavioral negative consequences, potentially hampering the development of children for years. However, its relationships with sleep electroencephalogram (EEG) have been scarcely investigated. Here, our main objective was to characterize the overnight EEG of OSA-affected children and its putative relationships with polysomnographic measures and cognitive functions. A two-step analysis involving 294 children (176 controls, 57% males, age range: 5-9 years) was conducted for this purpose. First, the activity and irregularity of overnight EEG spectrum were characterized in the typical frequency bands by means of relative spectral power and spectral entropy, respectively: δ (0.1-2 Hz), δ (2-4 Hz), θ (4-8 Hz), α (8-13 Hz), σ (10-16 Hz), β (13-19 Hz), β (19-30 Hz), and γ (30-70 Hz). Then, a correlation network analysis was conducted to evaluate relationships between them, six polysomnography variables (apnea-hypopnea index, respiratory arousal index, spontaneous arousal index, overnight minimum blood oxygen saturation, wake time after sleep onset, and sleep efficiency), and six cognitive scores (differential ability scales, Peabody picture vocabulary test, expressive vocabulary test, design copying, phonological processing, and tower test). We found that as the severity of the disease increases, OSA broadly affects sleep EEG to the point that the information from the different frequency bands becomes more similar, regardless of activity or irregularity. EEG activity and irregularity information from the most severely affected children were significantly associated with polysomnographic variables, which were coherent with both micro and macro sleep disruptions. We hypothesize that the EEG changes caused by OSA could be related to the occurrence of respiratory-related arousals, as well as thalamic inhibition in the slow oscillation generation due to increases in arousal levels aimed at recovery from respiratory events. Furthermore, relationships between sleep EEG and cognitive scores emerged regarding language, visual-spatial processing, and executive function with pronounced associations found with EEG irregularity in δ (Peabody picture vocabulary test and expressive vocabulary test maximum absolute correlations 0.61 and 0.54) and β (phonological processing, 0.74; design copying, 0.65; and Tow 0.52). Our results show that overnight EEG informs both sleep alterations and cognitive effects of pediatric OSA. Moreover, EEG irregularity provides new information that complements and expands the classic EEG activity analysis. These findings lay the foundation for the use of sleep EEG to assess cognitive changes in pediatric OSA.

摘要

小儿阻塞性睡眠呼吸暂停(OSA)是一种常见疾病,会干扰睡眠,并伴有神经认知和行为方面的负面后果,可能会在数年时间里阻碍儿童的发育。然而,其与睡眠脑电图(EEG)之间的关系鲜有研究。在此,我们的主要目标是描绘受OSA影响儿童的夜间脑电图特征,及其与多导睡眠图测量指标和认知功能之间的假定关系。为此,我们对294名儿童(176名对照儿童,57%为男性,年龄范围:5至9岁)进行了两步分析。首先,分别通过相对频谱功率和频谱熵,在典型频段中描绘夜间脑电图频谱的活动和不规则性:δ(0.1 - 2赫兹)、δ(2 - 4赫兹)、θ(4 - 8赫兹)、α(8 - 13赫兹)、σ(10 - 16赫兹)、β(13 - 19赫兹)、β(19 - 30赫兹)和γ(30 - 70赫兹)。然后,进行相关网络分析,以评估它们之间的关系、六个多导睡眠图变量(呼吸暂停低通气指数、呼吸唤醒指数、自发唤醒指数夜间最低血氧饱和度、睡眠开始后的清醒时间和睡眠效率)以及六个认知得分(差异能力量表、皮博迪图片词汇测试、表达性词汇测试、临摹设计、语音处理和塔测试)。我们发现,随着疾病严重程度的增加,OSA会广泛影响睡眠脑电图,以至于不同频段的信息变得更加相似,无论活动情况或不规则性如何。受影响最严重儿童的脑电图活动和不规则性信息与多导睡眠图变量显著相关,这与微观和宏观睡眠中断均相符。我们推测,OSA引起的脑电图变化可能与呼吸相关唤醒的发生有关,也与由于旨在从呼吸事件中恢复的唤醒水平增加而导致的慢振荡产生中的丘脑抑制有关。此外,睡眠脑电图与认知得分之间在语言、视觉空间处理和执行功能方面出现了关系,在δ频段(皮博迪图片词汇测试和表达性词汇测试的最大绝对相关性分别为0.61和0.54)和β频段(语音处理,0.74;临摹设计,0.65;塔测试,0.52)中发现了与脑电图不规则性的显著关联。我们的结果表明,夜间脑电图能够反映小儿OSA的睡眠改变和认知影响。此外,脑电图不规则性提供了新的信息,补充并扩展了经典的脑电图活动分析。这些发现为利用睡眠脑电图评估小儿OSA的认知变化奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3a/8595944/4d7e6c7558ec/fnins-15-644697-g001.jpg

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