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Failure of delayed feedback deep brain stimulation for intermittent pathological synchronization in Parkinson's disease.

PloS one | Mar 7, 2013

Suppression of excessively synchronous beta-band oscillatory activity in the brain is believed to suppress hypokinetic motor symptoms of Parkinson's disease. Recently, a lot of interest has been devoted to desynchronizing delayed feedback deep brain stimulation (DBS). This type of synchrony control was shown to destabilize the synchronized state in networks of simple model oscillators as well as in networks of coupled model neurons. However, the dynamics of the neural activity in Parkinson's disease exhibits complex intermittent synchronous patterns, far from the idealized synchronous dynamics used to study the delayed feedback stimulation. This study explores the action of delayed feedback stimulation on partially synchronized oscillatory dynamics, similar to what one observes experimentally in parkinsonian patients. We employ a computational model of the basal ganglia networks which reproduces experimentally observed fine temporal structure of the synchronous dynamics. When the parameters of our model are such that the synchrony is unphysiologically strong, the feedback exerts a desynchronizing action. However, when the network is tuned to reproduce the highly variable temporal patterns observed experimentally, the same kind of delayed feedback may actually increase the synchrony. As network parameters are changed from the range which produces complete synchrony to those favoring less synchronous dynamics, desynchronizing delayed feedback may gradually turn into synchronizing stimulation. This suggests that delayed feedback DBS in Parkinson's disease may boost rather than suppress synchronization and is unlikely to be clinically successful. The study also indicates that delayed feedback stimulation may not necessarily exhibit a desynchronization effect when acting on a physiologically realistic partially synchronous dynamics, and provides an example of how to estimate the stimulation effect.

Pubmed ID: 23469272 RIS Download

Mesh terms: Basal Ganglia | Deep Brain Stimulation | Humans | Hypokinesia | Male | Membrane Potentials | Models, Neurological | Nerve Net | Neurofeedback | Neurons | Parkinson Disease | Principal Component Analysis | Time Factors

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XPP-Aut: X-Windows Phase Plane plus Auto

XPPAUT is a tool for solving differential equations, difference equations, delay equations, functional equations, boundary value problems, and stochastic equations. It evolved from a chapter written by John Rinzel and me on the qualitative theory of nerve membranes and eventually became a commercial product for MSDOS computers called PHASEPLANE. It is now available as a program running under X11 and Windows. The code brings together a number of useful algorithms and is extremely portable. All the graphics and interface are written completely in Xlib which explains the somewhat idiosyncratic and primitive widgets interface. XPP contains the code for the popular bifurcation program, AUTO . Thus, you can switch back and forth between XPP and AUTO, using the values of one program in the other and vice-versa. I have put a ``friendly'' face on AUTO as well. You do not need to know much about it to play around with it. XPP has the capabilities for handling up to 590 differential equations. There are over a dozen solvers including several for stiff systems, a solver for integral equations and a symplectic solver. Up to 10 graphics windows can be visible at once and a variety of color combinations is supported. PostScript output is supported as well as GIF and animator GIF movies Post processing is easy and includes the ability to make histograms, FFTs and applying functions to columns of your data. Equilibria and linear stability as well as one-dimensional invariant sets can be computed. Nullclines and flow fields aid in the qualitative understanding of two-dimensional models. Poincare maps and equations on cylinders and tori are also supported. Some useful averaging theory tricks and various methods for dealing with coupled oscillators are included primarily because that is what I do for a living. Equations with Dirac delta functions are allowable. I have added an animation package that allows you to create animated versions of your simulations, such as a little pendulum moving back and forth or lamprey swimming. See toys! for examples. There is a curve-fitter based on the Marquardt-Levenberg algorithm which lets you fit data points to the solutions to dynamical systems. It is possible to automatically generate "movies'' of three-dimensional views of attractors or parametric changes in the attractor as some parameters vary. Dynamically link to external subroutines XPP has been successfully compiled on a SPARC II under OpenLook, a SPARC 1.5 running generic X, a NeXT running X11R4, a DEC 5000, a PC using Linux or Windows, and SGI and an HP 730. It also runs under Win95/NT/98 if you have an X-Server. I cannot vouch for other platforms but it has been compiled on the IBM RS6000. Building XPP requires only the standard C compiler, and Xlib. Look at the any README files that come with the distribution for solutions to common compilation problems.


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National Institutes of Health

NIH is the nations medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research. Helping to lead the way toward important medical discoveries that improve peoples health and save lives, NIH scientists investigate ways to prevent disease as well as the causes, treatments, and even cures for common and rare diseases. NIH research impacts: * child and teen health, * men's health, * minority health, * seniors' health, * women's health, and * wellness and lifestyle issues. Composed of 27 Institutes and Centers, the NIH provides leadership and financial support to researchers in every state and throughout the world.


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