Pharmaco-electroencephalography (EEG) is a non-invasive method used to assess the effects of pharmacological compounds on the central nervous system by processing the EEG signals which directly reveal the spontaneous synchronised postsynaptic neuronal activity of the cortex with high temporal resolution. The International Pharmaco-Encephalography Society (IPEG) has recently published guidelines, which were produced by a global panel of EEG experts, with the goal to increase the standardisation of pharmaco-EEG studies in human subjects and facilitate the comparability of data across laboratories, thus enabling data-pooling and meta-analyses. The recommended standard experimental procedure is to measure EEG activity under vigilance-controlled and resting conditions. The IPEG guidelines thoroughly present the technical details and therefore constitute a robust reference. The complementary aim of the present paper is to focus on practical aspects, pitfalls and precautions to be considered when processing pharmaco-EEG data by covering the following topics: (1) investigate the stability and reliability of 5-min EEG recordings under both vigilance-controlled and resting conditions; (2) assess the spontaneous time-dependent changes in spectral activity over time, and (3) apply the data-processing strategies suggested in the pharmaco-EEG guidelines and designed to optimally capture drug effects. For this purpose, the EEG data from a randomised, double-blind, crossover trial aimed at comparing the effect of diazepam (10 mg) and placebo in 16 healthy male volunteers is used to illustrate the discussion of the processing techniques and difficulties commonly faced when analysing pharmaco-EEG data.

1.
Fink M: Remembering the lost neuroscience of pharmaco-EEG. Acta Psychiatr Scand 2010;121:161-173.
2.
Stille G, Herrmann WM: Guidelines for pharmaco-EEG studies in man; in Herrmann WM (ed): Electroencephalography in Drug Research. Stuttgart, Fischer, 1982, pp 12-19.
3.
Dumermuth G, Ferber G, Herrmann WM, Hinrichs H, Künkel H: Recommendations for standardization of data acquisition and signal analysis in pharmaco-electroencephalography. Neuropsychobiology 1987;17:213-218.
4.
Herrmann WM, Abt K, Coppola R, Etevenon ET, Ferber G, Fink M, Gevins AS, Hinrichs H, Itil TM, John ER, Kubicki S, Künkel H, Kugler J, Lehmann D, Petsche H, Rappelsberger P, Röhmel J, Saito M, Saletu B, Scheuler W, Maurer K, Nuwer M; International Pharmaco-EEG Group (IPEG): Recommendations for EEG and evoked potential mapping. Neuropsychobiology 1989;22:170-176.
5.
Pivik RT, Broughton RJ, Coppola R, Davidson RJ, Fox N, Nuwer MR: Guidelines for the recording and quantitative analysis of electroencephalographic activity in research contexts. Psychophysiology 1993;30:547-558.
6.
Versavel M, Leonard JP, Herrmann WM, Böttcher M, Dietrich B, Jobert M, Oldigs-Kerber J, Ott H, Reimann IW, Schaffler K, Schulz H, Wauschkuku HC, Gallhofer B, Lehmann D, Sannita W: Standard Operating Procedure (SOP) for the registration and computer-supported evaluation of pharmaco-EEG data. Working Team ‘EEG in Phase I' of CIPS. Pharmacopsychiatry 1995;28:245-248.
7.
Jobert M, Wilson FJ, Ruigt GSF, Brunovsky M, Prichep LS, Drinkenburg WHIM, et al: Guidelines for the recording and evaluation of pharmaco-EEG data in man - International Pharmaco-EEG Society (IPEG). Neuropsychobiology 2012;66:201-220.
8.
Lilliefors H: On the Kolmogorov-Smirnov test for normality with mean and variance unknown. J Am Stat Assoc 1967;62:399-402.
9.
Rosenberger JL, Gasko M: Comparing location estimators - trimmed means, medians, and trimean; in Hoaglin DC, Mosteller F, Tukey JW (eds): Understanding Robust and Exploratory Data Analysis. New York, Wiley & Sons, 1983, pp 297-338.
10.
Gasser T, Bächer P, Möcks J: Transformations towards the normal distribution of broad band spectral parameters of the EEG. Electroencephalogr Clin Neurophysiol 1982;53:119-124.
11.
Koopman PAR, Wouters PAWM, Krijzer FNC: Mean power spectra from pharmaco-electrocorticographic studies: relative baseline correction and log transformation for a proper analysis of variance to assess drug effects. Neuropsychobiology 1996;33:100-105.
12.
Kiebel SJ, Tallon-Baudry C, Friston KJ: Parametric analysis of oscillatory activity as measured with EEG/MEG. Hum Brain Mapp 2005;26:170-177.
13.
Salinsky MC, Oken BS, Morehead L: Test-retest reliability in EEG frequency analysis. Electroencephalogr Clin Neurophysiol 1991;79:382-392.
14.
Gasser T, Bächer P, Steinberg H: Test-retest reliability of spectral parameters of the EEG. Electroencephalogr Clin Neurophysiol 1985;60:312-319.
15.
Näpflin M, Wildi M, Sarnthein J: Test-retest reliability of resting EEG spectra validates a statistical signature of persons. Clin Neurophysiol 2007;118:2519-2524.
16.
Jobert M, Schulz H, Jähnig P: On the choice of recording duration in pharmaco-EEG studies. Neuropsychobiology 1995;32:106-114.
17.
Olbrich S, Mulert C, Karch S, Trenner M, Leicht G, Pogarell O, Hegerl U: EEG-vigilance and BOLD effect during simultaneous EEG/fMRI measurement. Neuroimage 2009;45:319-332.
18.
Abt K: Descriptive data analysis: a concept between confirmatory and exploratory data analysis. Methods Inf Med 1987;26:77-88.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.