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


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 ? (4–7 Hz), a (7–14 Hz), ß (15–25 Hz), and ? (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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Optometry
Additional Information: © 2009 Wiley-Liss, Inc.
Uncontrolled Keywords: γ-amino butyric acid,oscillations,neuroimaging,magnetoencephalography,cortex,pharmacodynamic,gamma,beta,benzodiazipine,diazepam,Anatomy,Clinical Neurology,Radiology Nuclear Medicine and imaging,Neurology,Radiological and Ultrasound Technology
Publication ISSN: 1097-0193
Last Modified: 03 Jul 2024 07:03
Date Deposited: 27 Apr 2012 13:39
Full Text Link: http://onlineli ... .20889/abstract
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2010-04
Published Online Date: 2009-11-23
Authors: Hall, Stephen
Barnes, Gareth
Furlong, Paul (ORCID Profile 0000-0002-9840-8586)
Seri, Stefano (ORCID Profile 0000-0002-9247-8102)
Hillebrand, Arjan



Version: Published Version

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