UCLA Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, Los Angeles, California.
Telethon Kids Institute, University of Western Australia, Subiaco, Western Australia, Australia.
Autism Res. 2019 Dec;12(12):1758-1773. doi: 10.1002/aur.2193. Epub 2019 Aug 16.
Tuberous sclerosis complex (TSC) is a rare genetic disorder that confers a high risk for autism spectrum disorders (ASD), with behavioral predictors of ASD emerging early in life. Deviations in structural and functional neural connectivity are highly implicated in both TSC and ASD. For the first time, we explore whether electroencephalographic (EEG) measures of neural network function precede or predict the emergence of ASD in TSC. We determine whether altered brain function (a) is present in infancy in TSC, (b) differentiates infants with TSC based on ASD diagnostic status, and (c) is associated with later cognitive function. We studied 35 infants with TSC (N = 35), and a group of typically developing infants (N = 20) at 12 and 24 months of age. Infants with TSC were later subdivided into ASD and non-ASD groups based on clinical evaluation. We measured features of spontaneous alpha oscillations (6-12 Hz) that are closely associated with neural network development: alpha power, alpha phase coherence (APC), and peak alpha frequency (PAF). Infants with TSC demonstrated reduced interhemispheric APC compared to controls at 12 months of age, and these differences were found to be most pronounced at 24 months in the infants who later developed ASD. Across all infants, PAF at 24 months was associated with verbal and nonverbal cognition at 36 months. Associations between early network function and later neurodevelopmental and cognitive outcomes highlight the potential utility of early scalable EEG markers to identify infants with TSC requiring additional targeted intervention initiated very early in life. Autism Res 2019, 12: 1758-1773. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Approximately half of infants with tuberous sclerosis complex (TSC) develop autism. Here, using EEG, we find that there is a reduction in communication between brain regions during infancy in TSC, and that the infants who show the largest reductions are those who later develop autism. Being able to identify infants who show early signs of disrupted brain development may improve the timing of early prediction and interventions in TSC, and also help us to understand how early brain changes lead to autism.
结节性硬化症复合征（TSC）是一种罕见的遗传疾病，会增加自闭症谱系障碍（ASD）的风险，ASD 的行为预测因子在生命早期就出现了。结构和功能神经连接的偏差在 TSC 和 ASD 中都高度涉及。我们首次探索了脑电图（EEG）测量的神经网络功能是否先于或预测 TSC 中 ASD 的出现。我们确定了（a）在 TSC 婴儿中是否存在改变的大脑功能，（b）是否根据 ASD 诊断状态区分 TSC 婴儿，以及（c）是否与以后的认知功能相关。我们在 12 和 24 个月大时研究了 35 名 TSC 婴儿（N=35）和一组典型发育的婴儿（N=20）。根据临床评估，以后将 TSC 婴儿细分为 ASD 和非 ASD 组。我们测量了与神经网络发育密切相关的自发 alpha 振荡（6-12Hz）的特征：alpha 功率、alpha 相位相干性（APC）和峰值 alpha 频率（PAF）。与对照组相比，12 个月大的 TSC 婴儿表现出半球间 APC 降低，并且在以后发展为 ASD 的婴儿中，24 个月时的这些差异最为明显。在所有婴儿中，24 个月时的 PAF 与 36 个月时的言语和非言语认知相关。早期网络功能与以后的神经发育和认知结果之间的关联突出了早期可扩展 EEG 标志物的潜在效用，这些标志物可以识别需要在生命早期开始进行额外有针对性干预的 TSC 婴儿。自闭症研究 2019 年，12:1758-1773。 © 2019 自闭症研究国际协会，威利期刊，公司。 摘要：大约一半的结节性硬化症复合征（TSC）婴儿患有自闭症。在这里，我们使用脑电图发现，在婴儿期 TSC 中大脑区域之间的交流减少，并且显示最大减少的婴儿是那些以后发展为自闭症的婴儿。能够识别出显示早期大脑发育障碍迹象的婴儿可能会改善 TSC 中早期预测和干预的时机，并帮助我们了解早期大脑变化如何导致自闭症。
