Hypothesis & Theory ARTICLE

Front. Syst. Neurosci., 21 June 2011 | http://dx.doi.org/10.3389/fnsys.2011.00050

Chaotic desynchronization as the therapeutic mechanism of deep brain stimulation

Charles J. Wilson1*, Bryce Beverlin II2 and Theoden Netoff3
  • 1 Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA
  • 2 School of Physics and Astronomy, University of Minnesota, Minneapolis, MN, USA
  • 3 Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA

High frequency deep-brain stimulation of the subthalamic nucleus (deep brain stimulation, DBS) relieves many of the symptoms of Parkinson’s disease in humans and animal models. Although the treatment has seen widespread use, its therapeutic mechanism remains paradoxical. The subthalamic nucleus is excitatory, so its stimulation at rates higher than its normal firing rate should worsen the disease by increasing subthalamic excitation of the globus pallidus. The therapeutic effectiveness of DBS is also frequency and intensity sensitive, and the stimulation must be periodic; aperiodic stimulation at the same mean rate is ineffective. These requirements are not adequately explained by existing models, whether based on firing rate changes or on reduced bursting. Here we report modeling studies suggesting that high frequency periodic excitation of the subthalamic nucleus may act by desynchronizing the firing of neurons in the globus pallidus, rather than by changing the firing rate or pattern of individual cells. Globus pallidus neurons are normally desynchronized, but their activity becomes correlated in Parkinson’s disease. Periodic stimulation may induce chaotic desynchronization by interacting with the intrinsic oscillatory mechanism of globus pallidus neurons. Our modeling results suggest a mechanism of action of DBS and a pathophysiology of Parkinsonism in which synchrony, rather than firing rate, is the critical pathological feature.

Keywords: basal ganglia, deep brain stimulation, Parkinson’s disease

Citation: Wilson CJ, Beverlin B II and Netoff T (2011) Chaotic desynchronization as the therapeutic mechanism of deep brain stimulation. Front. Syst. Neurosci. 5:50. doi: 10.3389/fnsys.2011.00050

Received: 22 April 2011; Paper pending published: 23 May 2011;
Accepted: 05 June 2011; Published online: 21 June 2011.

Edited by:

James M. Tepper, Rutgers, The State University of New Jersey, USA

Reviewed by:

Thomas Wichman, Emory University, USA
Robert S. Turner, University of Pittsburgh, USA

Copyright: © 2011 Wilson, Beverlin II and Netoff. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Charles J. Wilson, Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA. e-mail: charles.wilson@utsa.edu