Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children's Hospital, Harvard Medical School, 1 Autumn Street, Boston, MA, 02215, USA.
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
J Neurodev Disord. 2019 Jul 31;11(1):15. doi: 10.1186/s11689-019-9275-z.
Rett syndrome is a neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene. Individuals with Rett syndrome typically develop normally until around 18 months of age before undergoing a developmental regression, and the disorder can lead to cognitive, motor, sensory, and autonomic dysfunction. Understanding the mechanism of developmental regression represents a unique challenge when viewed through a neuroscience lens. Are circuits that were previously established erased, and are new ones built to supplant old ones? One way to examine circuit-level changes is with the use of electroencephalography (EEG). Previous studies of the EEG in individuals with Rett syndrome have focused on morphological characteristics, but few have explored spectral power, including power as an index of brain function or disease severity. This study sought to determine if EEG power differs in girls with Rett syndrome and typically developing girls and among girls with Rett syndrome based on various clinical characteristics in order to better understand neural connectivity and cortical organization in individuals with this disorder.
Resting state EEG data were acquired from girls with Rett syndrome (n = 57) and typically developing children without Rett syndrome (n = 37). Clinical data were also collected for girls with Rett syndrome. EEG power across several brain regions in numerous frequency bands was then compared between girls with Rett syndrome and typically developing children and power in girls with Rett syndrome was compared based on these clinical measures. 1/ƒ slope was also compared between groups.
Girls with Rett syndrome demonstrate significantly lower power in the middle frequency bands across multiple brain regions. Additionally, girls with Rett syndrome that are postregression demonstrate significantly higher power in the lower frequency delta and theta bands and a significantly more negative slope of the power spectrum. Increased power in these bands, as well as a more negative 1/ƒ slope, trended with lower cognitive assessment scores.
Increased power in lower frequency bands is consistent with previous studies demonstrating a "slowing" of the background EEG in Rett syndrome. This increase, particularly in the delta band, could represent abnormal cortical inhibition due to dysfunctional GABAergic signaling and could potentially be used as a marker of severity due to associations with more severe Rett syndrome phenotypes.
雷特综合征是一种由 X 连锁 MECP2 基因突变引起的神经发育障碍。雷特综合征患者通常在 18 个月左右之前发育正常，然后出现发育倒退，该疾病可导致认知、运动、感觉和自主功能障碍。从神经科学的角度来看，理解发育倒退的机制是一个独特的挑战。以前建立的回路是否被抹去，而新的回路是否被建立来取代旧的回路？一种检查回路水平变化的方法是使用脑电图（EEG）。以前对雷特综合征患者脑电图的研究集中在形态特征上，但很少有研究探索频谱功率，包括作为大脑功能或疾病严重程度指标的功率。本研究旨在确定雷特综合征女孩与正常发育女孩以及基于各种临床特征的雷特综合征女孩的脑电图功率是否不同，以便更好地了解该疾病患者的神经连接和皮质组织。
从雷特综合征女孩（n=57）和无雷特综合征的正常发育女孩（n=37）中获取静息状态脑电图数据。还收集了雷特综合征女孩的临床数据。然后比较了雷特综合征女孩和正常发育女孩在多个频带的多个脑区的脑电图功率，并根据这些临床指标比较了雷特综合征女孩的脑电图功率。还比较了两组之间的 1/ƒ 斜率。
雷特综合征女孩在多个脑区的中频带显示出明显较低的功率。此外，处于退行期后的雷特综合征女孩在较低的频率 delta 和 theta 波段显示出明显更高的功率，以及明显更负的功率谱斜率。这些波段的功率增加，以及更负的 1/ƒ 斜率，与认知评估分数较低呈趋势相关。
较低频带的功率增加与以前的研究一致，表明雷特综合征中背景 EEG 变慢。这种增加，特别是在 delta 波段，可能由于 GABA 能信号传导功能障碍导致异常皮质抑制，并可能由于与更严重的雷特综合征表型相关而作为严重程度的标志物。
