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

Dovzhenok A, Park C, Worth RM, Rubchinsky LL - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematical Sciences and Center for Mathematical Biosciences, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America. andrey.dovzhenok@uc.edu

ABSTRACT
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.

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Change in the number of PCA components in the network with different feedback stimulation set-ups.Positive change indicates dynamics less synchronous than pre-stimulation dynamics, negative change indicates more coherent dynamics. Two different spatial stimulation set-ups and two different weights are presented. A, B) 50% or 70% of STN neurons are directly affected by stimulation current, correspondingly. Electrodes are placed near the 5th and 7th STN neurons in the array. C, D) 50% or 70% of STN neurons are directly affected by stimulation current, correspondingly. Electrodes are placed near the 5th, 6th and 7th STN neurons. Weight parameters are w1 = 0.3, A, C) w2 = 0; B, D) w2 = 0.1. Iapp = 5 in all simulations.
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pone-0058264-g005: Change in the number of PCA components in the network with different feedback stimulation set-ups.Positive change indicates dynamics less synchronous than pre-stimulation dynamics, negative change indicates more coherent dynamics. Two different spatial stimulation set-ups and two different weights are presented. A, B) 50% or 70% of STN neurons are directly affected by stimulation current, correspondingly. Electrodes are placed near the 5th and 7th STN neurons in the array. C, D) 50% or 70% of STN neurons are directly affected by stimulation current, correspondingly. Electrodes are placed near the 5th, 6th and 7th STN neurons. Weight parameters are w1 = 0.3, A, C) w2 = 0; B, D) w2 = 0.1. Iapp = 5 in all simulations.

Mentions: On the contrary, in the intermittent regime the same delayed feedback stimulation results in no apparent change in synchronization for moderate stimulation strengths, while stronger stimulation, in fact, leads to increased synchronization among STN neurons (Figure 4B). While Figure 4B illustrates the dynamics of two neurons in the network, the synchronizing effect of the “desynchronizing” feedback stimulation is confirmed by the decrease in the number of principal components for the whole network as can be seen in Figure 5.


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

Dovzhenok A, Park C, Worth RM, Rubchinsky LL - PLoS ONE (2013)

Change in the number of PCA components in the network with different feedback stimulation set-ups.Positive change indicates dynamics less synchronous than pre-stimulation dynamics, negative change indicates more coherent dynamics. Two different spatial stimulation set-ups and two different weights are presented. A, B) 50% or 70% of STN neurons are directly affected by stimulation current, correspondingly. Electrodes are placed near the 5th and 7th STN neurons in the array. C, D) 50% or 70% of STN neurons are directly affected by stimulation current, correspondingly. Electrodes are placed near the 5th, 6th and 7th STN neurons. Weight parameters are w1 = 0.3, A, C) w2 = 0; B, D) w2 = 0.1. Iapp = 5 in all simulations.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585780&req=5

pone-0058264-g005: Change in the number of PCA components in the network with different feedback stimulation set-ups.Positive change indicates dynamics less synchronous than pre-stimulation dynamics, negative change indicates more coherent dynamics. Two different spatial stimulation set-ups and two different weights are presented. A, B) 50% or 70% of STN neurons are directly affected by stimulation current, correspondingly. Electrodes are placed near the 5th and 7th STN neurons in the array. C, D) 50% or 70% of STN neurons are directly affected by stimulation current, correspondingly. Electrodes are placed near the 5th, 6th and 7th STN neurons. Weight parameters are w1 = 0.3, A, C) w2 = 0; B, D) w2 = 0.1. Iapp = 5 in all simulations.
Mentions: On the contrary, in the intermittent regime the same delayed feedback stimulation results in no apparent change in synchronization for moderate stimulation strengths, while stronger stimulation, in fact, leads to increased synchronization among STN neurons (Figure 4B). While Figure 4B illustrates the dynamics of two neurons in the network, the synchronizing effect of the “desynchronizing” feedback stimulation is confirmed by the decrease in the number of principal components for the whole network as can be seen in Figure 5.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematical Sciences and Center for Mathematical Biosciences, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America. andrey.dovzhenok@uc.edu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus