Cortical EEG oscillations and network connectivity as efficacy indices for assessing drugs with cognition enhancing potential
Cortical EEG oscillations and network connectivity as efficacy indices for assessing drugs with cognition enhancing potential
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DOI：
10.1016/j.neuropharm.2014.08.015
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发表时间：
2014-11-01
影响因子：
4.7
通讯作者：
Drinkenburg, W. H. I. M.
中科院分区：
文献类型：
--
作者：
Ahnaou, A.;Huysmans, H.;Drinkenburg, W. H. I. M.
脑电图（EEG）振荡的同步代表了皮质和皮质下网络的核心机制，神经同步的紊乱是神经系统和神经精神疾病认知处理缺陷的基础。在这里，我们研究了认知增强剂（多奈哌齐、卡巴拉汀、他克林、加兰他敏和美金刚）对长期在不同皮质区域使用硬膜外电极的清醒大鼠的脑电图振荡和网络连接的影响，这些药物被批准用于痴呆症的对症治疗。接下来，对毒蕈碱受体拮抗剂东莨菪碱造成的认知障碍的脑电图网络指数进行了建模。最后，我们检查了认知增强剂使这些异常振荡正常化的功效。认知增强剂引起与较低活动水平相关的皮层慢θ（4.5-6赫兹）和伽马（30.5-50赫兹）振荡的系统（“指纹”）增强。主成分分析 (PCA) 揭示了一个紧凑的簇，与不同的药物类别相比，它对应于共享的潜在机制。功能网络连接显示顶枕叶和半球间皮层区域之间一致的一致的慢θ活动升高。在装有深度海马 CA1-CA3 电极的大鼠中，多奈哌齐在皮质海马网络中引发了类似的振荡和连贯活动。当与东莨菪碱联合使用时，认知增强剂减弱了相干慢δ活动的左移。脑电图一致性持续转变为与慢θ和γ振荡改变相关的慢振荡可能是东莨菪碱治疗动物认知缺陷的基础，而增强的相干慢θ和γ活动可能是认知增强剂对可塑性和认知过程发挥有益作用的相关机制。研究结果强调，PCA 和网络连接是评估具有认知增强潜力的新型治疗药物疗效的宝贵工具。 (C) 2014 Elsevier Ltd. 保留所有权利。
Synchronization of electroencephalographic (EEG) oscillations represents a core mechanism for cortical and subcortical networks, and disturbance in neural synchrony underlies cognitive processing deficits in neurological and neuropsychiatric disorders. Here, we investigated the effects of cognition enhancers (donepezil, rivastigmine, tacrine, galantamine and memantine), which are approved for symptomatic treatment of dementia, on EEG oscillations and network connectivity in conscious rats chronically instrumented with epidural electrodes in different cortical areas. Next, EEG network indices of cognitive impairments with the muscarinic receptor antagonist scopolamine were modeled. Lastly, we examined the efficacy of cognition enhancers to normalize those aberrant oscillations.Cognition enhancers elicited systematic ("fingerprint") enhancement of cortical slow theta (4.5 - 6 Hz) and gamma (30.5-50 Hz) oscillations correlated with lower activity levels. Principal component analysis (PCA) revealed a compact cluster that corresponds to shared underlying mechanisms as compared to different drug classes. Functional network connectivity revealed consistent elevated coherent slow theta activity in parieto-occipital and between interhemispheric cortical areas. In rats instrumented with depth hippocampal CA1-CA3 electrodes, donepezil elicited similar oscillatory and coherent activities in cortico-hippocampal networks. When combined with scopolamine, the cognition enhancers attenuated the leftward shift in coherent slow delta activity. Such a consistent shift in EEG coherence into slow oscillations associated with altered slow theta and gamma oscillations may underlie cognitive deficits in scopolamine-treated animals, whereas enhanced coherent slow theta and gamma activity may be a relevant mechanism by which cognition enhancers exert their beneficial effect on plasticity and cognitive processes. The findings underscore that PCA and network connectivity are valuable tools to assess efficacy of novel therapeutic drugs with cognition enhancing potential. (C) 2014 Elsevier Ltd. All rights reserved.