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Multielectrode array analysis of EEG biomarkers in a mouse model of Fragile X Syndrome.
Neurobiology of Disease ( IF 5.1 ) Pub Date : 2020-02-06 , DOI: 10.1016/j.nbd.2020.104794
Carrie R Jonak 1 , Jonathan W Lovelace 2 , Iryna M Ethell 3 , Khaleel A Razak 4 , Devin K Binder 3
Affiliation  

Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent EEG studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced inter-trial phase coherence of sound-evoked gamma oscillations. Identification of comparable EEG biomarkers in mouse models of FXS could facilitate the pre-clinical to clinical therapeutic pipeline. However, while human EEG studies have involved 128-channel scalp EEG acquisition, no mouse studies have been performed with more than three EEG channels. In the current study, we employed a recently developed 30-channel mouse multielectrode array (MEA) system to record and analyze resting and stimulus-evoked EEG signals in WT vs. Fmr1 KO mice. Using this system, we now report robust MEA-derived phenotypes including higher resting EEG power, altered event-related potentials (ERPs) and reduced inter-trial phase coherence to auditory chirp stimuli in Fmr1 KO mice that are remarkably similar to those reported in humans with FXS. We propose that the MEA system can be used for: (i) derivation of higher-level EEG parameters; (ii) EEG biomarkers for drug testing; and (ii) mechanistic studies of FXS pathophysiology.

中文翻译:

脆性 X 综合征小鼠模型中 EEG 生物标志物的多电极阵列分析。

脆性 X 综合征 (FXS) 是导致智力障碍的主要已知遗传原因,其症状包括焦虑增加以及社交和感觉处理缺陷。最近对 FXS 患者的脑电图研究发现,神经振荡缺陷包括静息状态伽马功率增加、听觉诱发电位幅度增加以及声音诱发伽马振荡的试验间相位相干性降低。在 FXS 小鼠模型中鉴定可比较的 EEG 生物标志物可以促进临床前到临床治疗管道。然而,虽然人类脑电图研究涉及 128 通道头皮脑电图采集,但尚未对超过三个脑电图通道进行小鼠研究。在目前的研究中,我们采用了最近开发的 30 通道小鼠多电极阵列 (MEA) 系统来记录和分析 WT 与 Fmr1 KO 小鼠的静息和刺激诱发的 EEG 信号。使用这个系统,我们现在报告了强大的 MEA 衍生表型,包括更高的静息脑电图功率、改变的事件相关电位 (ERPs) 和 Fmr1 KO 小鼠中与听觉啁啾刺激的试验间相干性降低,这与人类报道的非常相似与 FXS。我们建议 MEA 系统可用于: (i) 推导更高级别的 EEG 参数;(ii) 用于药物测试的脑电图生物标志物;(ii) FXS 病理生理学的机制研究。在 Fmr1 KO 小鼠中,事件相关电位 (ERPs) 改变并降低了与听觉啁啾刺激的试验间相干性,这与人类 FXS 报告的那些非常相似。我们建议 MEA 系统可用于: (i) 推导更高级别的 EEG 参数;(ii) 用于药物测试的脑电图生物标志物;(ii) FXS 病理生理学的机制研究。在 Fmr1 KO 小鼠中,事件相关电位 (ERPs) 改变并降低了与听觉啁啾刺激的试验间相干性,这与人类 FXS 报告的那些非常相似。我们建议 MEA 系统可用于: (i) 推导更高级别的 EEG 参数;(ii) 用于药物测试的脑电图生物标志物;(ii) FXS 病理生理学的机制研究。
更新日期:2020-02-07
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