Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco-magnetoencephalography.

Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco-magnetoencephalography.
复制标题

使用药物脑磁图确定人类皮质中 GABA 能调节的神经网络药效学。

DOI:
10.1002/hbm.20889
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发表时间:
2010-04
影响因子:
4.8
通讯作者:
Hillebrand, Arjan
Hillebrand, Arjan
中科院分区:
医学2区
文献类型:
--
作者:
Hall, Stephen D.;Barnes, Gareth R.;Furlong, Paul L.;Seri, Stefano;Hillebrand, Arjan

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神经网络振荡是神经科学研究中的一种统一现象,具有跨尺度和物种的可比测量。皮质振荡在表征健康和疾病中的神经元网络功能中具有核心重要性,并且在有效药物开发中具有影响力。虽然动物在体外和体内的电生理学是能够表征神经元活动的神经元诱导的调制,目前的人类同行有空间和时间的限制。因此,人类等效物的潜在应用是广泛的。在这里,我们展示了一种新的当代神经成像方法,称为药物脑磁图。这种方法确定了空间分布的神经元网络振荡功率变化后,药物管理和重建这些调制的时间过程中,在关注的焦点区域。作为一个概念的证明,我们的特点是非特异性GABA能调节剂地西泮,它具有广泛的治疗应用。我们证明,地西泮不同地调节皮质特定区域的θ(4-7 Hz)、α(7-14 Hz)、β(15-25 Hz)和γ(30-80 Hz)频率振荡,其药效学特征与药物摄取一致。我们研究这些结果的相关性,从其他方式和地西泮的各种治疗后果的空间和时间的观察,并讨论了这种方法在药物开发和转化神经科学方面的潜在应用。^Brain Mapp,2010.© 2009 Wiley利斯公司
Neuronal network oscillations are a unifying phenomenon in neuroscience research, with comparable measurements across scales and species. Cortical oscillations are of central importance in the characterization of neuronal network function in health and disease and are influential in effective drug development. Whilst animal in vitro and in vivo electrophysiology is able to characterize pharmacologically induced modulations in neuronal activity, present human counterparts have spatial and temporal limitations. Consequently, the potential applications for a human equivalent are extensive. Here, we demonstrate a novel implementation of contemporary neuroimaging methods called pharmaco‐magnetoencephalography. This approach determines the spatial profile of neuronal network oscillatory power change across the cortex following drug administration and reconstructs the time course of these modulations at focal regions of interest. As a proof of concept, we characterize the nonspecific GABAergic modulator diazepam, which has a broad range of therapeutic applications. We demonstrate that diazepam variously modulates θ (4–7 Hz), α (7–14 Hz), β (15–25 Hz), and γ (30–80 Hz) frequency oscillations in specific regions of the cortex, with a pharmacodynamic profile consistent with that of drug uptake. We examine the relevance of these results with regard to the spatial and temporal observations from other modalities and the various therapeutic consequences of diazepam and discuss the potential applications of such an approach in terms of drug development and translational neuroscience. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
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影响因子: 3.1
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