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Cross-conditional entropy and coherence analysis of pharmaco-EEG changes induced by alprazolam

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Abstract

Rationale

Quantitative analysis of electroencephalographic signals (EEG) and their interpretation constitute a helpful tool in the assessment of the bioavailability of psychoactive drugs in the brain. Furthermore, psychotropic drug groups have typical signatures which relate biochemical mechanisms with specific EEG changes.

Objectives

To analyze the pharmacological effect of a dose of alprazolam on the connectivity of the brain during wakefulness by means of linear and nonlinear approaches.

Methods

EEG signals were recorded after alprazolam administration in a placebo-controlled crossover clinical trial. Nonlinear couplings assessed by means of corrected cross-conditional entropy were compared to linear couplings measured with the classical magnitude squared coherence.

Results

Linear variables evidenced a statistically significant drug-induced decrease, whereas nonlinear variables showed significant increases. All changes were highly correlated to drug plasma concentrations. The spatial distribution of the observed connectivity changes clearly differed from a previous study: changes before and after the maximum drug effect were mainly observed over the anterior half of the scalp. Additionally, a new variable with very low computational cost was defined to evaluate nonlinear coupling. This is particularly interesting when all pairs of EEG channels are assessed as in this study.

Conclusions

Results showed that alprazolam induced changes in terms of uncoupling between regions of the scalp, with opposite trends depending on the variables: decrease in linear ones and increase in nonlinear features. Maps provided consistent information about the way brain changed in terms of connectivity being definitely necessary to evaluate separately linear and nonlinear interactions.

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Acknowledgment

The authors would like to thank Naira P. Martínez for her help with the preliminary results. They would also like to dedicate this publication to the memory of Professor Manel Barbanoj, a brilliant scientist and mentor and a good friend.

CIBER-BBN is an initiative of the Instituto de Salud Carlos III, Spain. This study was supported in part by the Subdirección General de Proyectos de Investigación, Ministerio de Ciencia e Innovación, Spain, under contract TEC2008-02754/TEC.

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Authors and Affiliations

  1. Department of Automatic Control (ESAII), Biomedical Engineering Research Centre (CREB), Universitat Politècnica de Catalunya (UPC), Carrer Pau Gargallo 5, 08028, Barcelona, Spain

    J. F. Alonso, M. A. Mañanas, S. Romero & M. Rojas-Martínez

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

    J. F. Alonso, M. A. Mañanas, S. Romero & M. Rojas-Martínez

  3. Human Experimental Neuropsychopharmacology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau (HSCSP), Barcelona, Spain

    J. Riba

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

    J. Riba

  5. CIBER de Salud Mental (CIBERSAM), Madrid, Spain

    J. Riba

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  1. J. F. Alonso
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  2. M. A. Mañanas
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  3. S. Romero
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  4. M. Rojas-Martínez
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  5. J. Riba
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Correspondence to J. F. Alonso.

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Alonso, J.F., Mañanas, M.A., Romero, S. et al. Cross-conditional entropy and coherence analysis of pharmaco-EEG changes induced by alprazolam. Psychopharmacology 221, 397–406 (2012). https://doi.org/10.1007/s00213-011-2587-7

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  • DOI: https://doi.org/10.1007/s00213-011-2587-7

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