Research Article

Drug effect on EEG connectivity assessed by linear and nonlinear couplings

  1. Joan F. Alonso1,2,*,
  2. Miguel A. Mañanas1,2,
  3. Sergio Romero1,2,
  4. Dirk Hoyer3,
  5. Jordi Riba4,5,6,
  6. Manel J. Barbanoj4,5,6

Article first published online: 5 NOV 2009

DOI: 10.1002/hbm.20881

Issue

Human Brain Mapping

Human Brain Mapping

Volume 31, Issue 3, pages 487–497, March 2010

Additional Information

How to Cite

Alonso, J. F., Mañanas, M. A., Romero, S., Hoyer, D., Riba, J. and Barbanoj, M. J. (2010), Drug effect on EEG connectivity assessed by linear and nonlinear couplings. Hum. Brain Mapp., 31: 487–497. doi: 10.1002/hbm.20881

Author Information

  1. 1

    Biomedical Engineering Research Center, Department of Automatic Control, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain

  2. 2

    CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain

  3. 3

    Department of Neurology, Biomagnetic Centre, Friedrich Schiller University, Jena, Germany

  4. 4

    Drug Research Center, Hospital de la Santa Creu i Sant Pau (HSCSP), Barcelona, Spain

  5. 5

    Department of Pharmacology and Therapeutics, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

  6. 6

    CIBER de Salud Mental (CIBERSAM), Spain

*Department of Automatic Control (ESAII), Biomedical Engineering Research Center (CREB), Universitat Politècnica de Catalunya (UPC), Carrer Pau Gargallo5, 08028 Barcelona, Spain

Publication History

  1. Issue published online: 12 FEB 2010
  2. Article first published online: 5 NOV 2009
  3. Manuscript Accepted: 20 JUL 2009
  4. Manuscript Revised: 3 JUL 2009
  5. Manuscript Received: 19 DEC 2008

Funded by

  • Subdirección General de Proyectos de Investigación, Ministerio de Ciencia e Innovación, Spain. Grant Number: TEC2008-02754/TEC
  • Deutsche Forschungsgemeinschaft (DFG), Germany. Grant Number: DH 1634/12-2

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Keywords:

  • alprazolam;
  • benzodiazepine;
  • drug effect;
  • EEG;
  • mutual information

Abstract

Quantitative analysis of human electroencephalogram (EEG) is a valuable method for evaluating psychopharmacological agents. Although the effects of different drug classes on EEG spectra are already known, interactions between brain locations remain unclear. In this work, cross mutual information function and appropriate surrogate data were applied to assess linear and nonlinear couplings between EEG signals. The main goal was to evaluate the pharmacological effects of alprazolam on brain connectivity during wakefulness in healthy volunteers using a cross-over, placebo-controlled design. Eighty-five pairs of EEG leads were selected for the analysis, and connectivity was evaluated inside anterior, central, and posterior zones of the scalp. Connectivity between these zones and interhemispheric connectivity were also measured. Results showed that alprazolam induced significant changes in EEG connectivity in terms of information transfer in comparison with placebo. Trends were opposite depending on the statistical characteristics: decreases in linear connectivity and increases in nonlinear couplings. These effects were generally spread over the entire scalp. Linear changes were negatively correlated, and nonlinear changes were positively correlated with drug plasma concentrations; the latter showed higher correlation coefficients. The use of both linear and nonlinear approaches revealed the importance of assessing changes in EEG connectivity as this can provide interesting information about psychopharmacological effects. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc.

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