Failure of Delayed Feedback Deep Brain Stimulation for Intermittent Pathological Synchronization in Parkinson's Disease

TL;DR

This study investigates the effectiveness of delayed feedback deep brain stimulation in Parkinson's disease, revealing it may inadvertently increase neural synchrony in realistic, intermittent oscillatory patterns, challenging its clinical utility.

Contribution

The paper demonstrates that delayed feedback DBS can enhance synchronization in physiologically realistic models, highlighting limitations of this approach for Parkinson's treatment.

Findings

Delayed feedback can desynchronize overly synchronized networks.

In realistic models, delayed feedback may increase neural synchrony.

Effectiveness of feedback stimulation depends on network parameters.

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 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.