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

Stephen Hall, Gareth Barnes, Paul Furlong, Stefano Seri, Arjan Hillebrand

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Article number19937723
Pages (from-to)581-594
Number of pages14
JournalHuman Brain Mapping
Volume31
Issue number4
Early online date23 Nov 2009
DOIs
Publication statusPublished - Apr 2010

Bibliographical note

© 2009 Wiley-Liss, Inc.

Keywords

  • γ-amino butyric acid
  • oscillations
  • neuroimaging
  • magnetoencephalography
  • cortex
  • pharmacodynamic
  • gamma
  • beta
  • benzodiazipine
  • diazepam

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