期刊
HUMAN BRAIN MAPPING
卷 31, 期 4, 页码 581-594出版社
WILEY
DOI: 10.1002/hbm.20889
关键词
gamma-amino butyric acid; oscillations; neuroimaging; magnetoencephalography; cortex; pharmacodynamic; gamma; beta; benzodiazipine; diazepam
资金
- Research Councils
- United Kingdom
- Wellcome Trust
- Dr. Hadwen Trust
- Lord Dowding Fund
- Biotechnology and Biological Sciences Research Council [BB/H003894/1] Funding Source: researchfish
- BBSRC [BB/H003894/1] Funding Source: UKRI
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 theta (4-7 Hz), alpha (7-14 Hz), beta (15-25 Hz), and gamma (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 31:581-594, 2010. (C) 2009 Wiley-Liss, Inc.
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