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Therapeutic rewiring by means of desynchronizing brain stimulation

In a mathematical model we show that the dynamical multi-stability of a network of bursting subthalamic neurons, caused by synaptic plasticity, has strong impact on the stimulus-response properties when exposed to desynchronizing coordinated reset (CR) stimulation. Such stimuli can reliably shift the network from a stable state with pathological synchrony and connectivity to a stable desynchronized state with down-regulated connectivity.

Finally, the desynchronizing stimulation protocol is tested in two experimental setups: first, we studied long-lasting effects of CR stimulation in rat hippocampal slice rendered epileptic by magnesium withdrawal. We show that the CR stimulation causes a long-lasting desynchronization between hippocampal neuronal populations together with a widespread decrease of the amplitude of the epileptiform activity. In contrast, periodic stimulation control stimulation induces a long-lasting increase of both synchronization and amplitude. Second, we developed appropriate hardware enabling a clinical pilot-study applying coordinated reset stimulation through externalized DBS electrodes to patients suffering from Parkinson's disease. CR stimulation resulted in a long-lasting reduction of the symptoms depicted by clinical motor scores. These theoretical and experimental findings support the idea that desynchronizing stimulation can induce long-lasting effects in neuronal networks featuring dynamical multi-stability.

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Correspondence to Christian Hauptmann.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Hippocampal Slice
  • Motor Score
  • Stimulation Protocol
  • Epileptiform Activity
  • Control Stimulation