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Licensed Unlicensed Requires Authentication Published by De Gruyter February 18, 2015

How does spreading depression spread? Physiology and modeling

  • Bas-Jan Zandt ORCID logo EMAIL logo , Bennie ten Haken , Michel J.A.M. van Putten and Markus A. Dahlem


Spreading depression (SD) is a wave phenomenon in gray matter tissue. Locally, it is characterized by massive redistribution of ions across cell membranes. As a consequence, there is sustained membrane depolarization and tissue polarization that depress any normal electrical activity. Despite these dramatic events, SD remains difficult to observe in humans noninvasively, which, for long, has slowed advances in this field. The growing appreciation of its clinical importance in migraine and stroke is therefore consistent with an increasing need for computational methods that tackle the complexity of the problem at multiple levels. In this review, we focus on mathematical tools to investigate the question of spread and its two complementary aspects: What are the physiological mechanisms and what is the spatial extent of SD in the cortex? This review discusses two types of models used to study these two questions, namely, Hodgkin-Huxley type and generic activator-inhibitor models, and the recent advances in techniques to link them.

Corresponding author: Bas-Jan Zandt, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Postboks 7800, N-5020 Bergen, Norway, e-mail: .


The authors thank the Fields Institute for hosting the workshop on Cortical Spreading Depression and Related Neurological Phenomena, allowing us to incorporate new recent insights in this review.


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Received: 2014-10-6
Accepted: 2014-10-31
Published Online: 2015-2-18
Published in Print: 2015-4-1

©2015 by De Gruyter

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