The lack of robust and reliable clinical biomarkers in Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, has limited the successful translation of bench-to-bedside therapeutics. While numerous drugs have shown promise in reversing synaptic and behavioral phenotypes in mouse models of FXS, none have demonstrated clinical efficacy in humans. Electroencephalographic (EEG) measures have been identified as candidate biomarkers as EEG recordings of both adults with FXS and mouse models of FXS consistently exhibit alterations in resting state and task-related activity. However, the developmental timing of these EEG differences is not known as thus far EEG studies have not focused on young children with FXS. Further, understanding how EEG differences are associated with core symptoms of FXS is crucial to successful use of EEG as a biomarker, and may improve our understanding of the disorder. Resting-state EEG was collected from FXS boys with full mutation of Fmr1 (2.5–7 years old, n = 11) and compared with both age-matched (n = 12) and cognitive-matched (n = 12) typically developing boys. Power spectra (including aperiodic and periodic components) were compared using non-parametric cluster-based permutation testing. Associations between 30 and 50 Hz gamma power and cognitive, language, and behavioral measures were evaluated using Pearson correlation and linear regression with age as a covariate. FXS participants showed increased power in the beta/gamma range (~ 25–50 Hz) across multiple brain regions. Both a reduction in the aperiodic (1/f) slope and increase in beta/gamma periodic activity contributed to the significant increase in high-frequency power. Increased gamma power, driven by the aperiodic component, was associated with better language ability in the FXS group. No association was observed between gamma power and parent report measures of behavioral challenges, sensory hypersensitivities, or adaptive behaviors. The study sample size was small, although comparable to other human studies in rare-genetic disorders. Findings are also limited to males in the age range studied. Resting-state EEG measures from this study in young boys with FXS identified similar increases in gamma power previously reported in adults and mouse models. The observed positive association between resting state aperiodic gamma power and language development supports hypotheses that alterations in some EEG measures may reflect ongoing compensatory mechanisms.

中文翻译：

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患有脆性 X 综合征的年轻男孩的非周期性伽马能量增加与更好的语言能力有关

脆性 X 综合征 (FXS) 是智力障碍最常见的遗传形式，但缺乏稳健可靠的临床生物标志物，这限制了临床到床边疗法的成功转化。虽然许多药物在 FXS 小鼠模型中显示出逆转突触和行为表型的前景，但没有一种药物在人类中表现出临床疗效。脑电图 (EEG) 测量已被确定为候选生物标志物，因为成人 FXS 和 FXS 小鼠模型的 EEG 记录始终表现出静息状态和任务相关活动的改变。然而，这些脑电图差异的发展时间尚不清楚，因为迄今为止脑电图研究尚未关注患有 FXS 的幼儿。更远，了解 EEG 差异如何与 FXS 的核心症状相关对于成功使用 EEG 作为生物标志物至关重要，并且可能会提高我们对这种疾病的理解。从 Fmr1 完全突变的 FXS 男孩（2.5-7 岁，n = 11）收集静息态脑电图，并与年龄匹配（n = 12）和认知匹配（n = 12）的典型发育男孩进行比较。使用基于非参数集群的置换测试来比较功率谱（包括非周期性和周期性分量）。使用 Pearson 相关和线性回归以年龄作为协变量评估 30 和 50 Hz 伽马功率与认知、语言和行为测量之间的关联。FXS 参与者在多个大脑区域的 beta/gamma 范围（~ 25-50 Hz）中表现出增加的功率。非周期性 (1/f) 斜率的降低和 β/γ 周期性活动的增加都有助于高频功率的显着增加。由非周期性成分驱动的伽马功率增加与 FXS 组更好的语言能力有关。没有观察到伽马功率和父母报告的行为挑战、感觉超敏反应或适应性行为之间的关联。尽管与其他罕见遗传疾病的人类研究相当，但研究样本量很小。结果也仅限于所研究年龄范围内的男性。这项研究对患有 FXS 的年轻男孩的静息状态 EEG 测量发现了先前在成人和小鼠模型中报告的伽马功率的类似增加。