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Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation

Excessive neuronal synchrony is a hallmark of neurological disorders such as epilepsy and Parkinson's disease. An established treatment for medically refractory Parkinson's disease is high-frequency (HF) deep brain stimulation (DBS). However, symptoms return shortly after cessation of HF-D...

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Autores principales: Khaledi-Nasab, Ali, Kromer, Justus A., Tass, Peter A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893102/
https://www.ncbi.nlm.nih.gov/pubmed/33613303
http://dx.doi.org/10.3389/fphys.2020.622620
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author Khaledi-Nasab, Ali
Kromer, Justus A.
Tass, Peter A.
author_facet Khaledi-Nasab, Ali
Kromer, Justus A.
Tass, Peter A.
author_sort Khaledi-Nasab, Ali
collection PubMed
description Excessive neuronal synchrony is a hallmark of neurological disorders such as epilepsy and Parkinson's disease. An established treatment for medically refractory Parkinson's disease is high-frequency (HF) deep brain stimulation (DBS). However, symptoms return shortly after cessation of HF-DBS. Recently developed decoupling stimulation approaches, such as Random Reset (RR) stimulation, specifically target pathological connections to achieve long-lasting desynchronization. During RR stimulation, a temporally and spatially randomized stimulus pattern is administered. However, spatial randomization, as presented so far, may be difficult to realize in a DBS-like setup due to insufficient spatial resolution. Motivated by recently developed segmented DBS electrodes with multiple stimulation sites, we present a RR stimulation protocol that copes with the limited spatial resolution of currently available depth electrodes for DBS. Specifically, spatial randomization is realized by delivering stimuli simultaneously to L randomly selected stimulation sites out of a total of M stimulation sites, which will be called L/M-RR stimulation. We study decoupling by L/M-RR stimulation in networks of excitatory integrate-and-fire neurons with spike-timing dependent plasticity by means of theoretical and computational analysis. We find that L/M-RR stimulation yields parameter-robust decoupling and long-lasting desynchronization. Furthermore, our theory reveals that strong high-frequency stimulation is not suitable for inducing long-lasting desynchronization effects. As a consequence, low and high frequency L/M-RR stimulation affect synaptic weights in qualitatively different ways. Our simulations confirm these predictions and show that qualitative differences between low and high frequency L/M-RR stimulation are present across a wide range of stimulation parameters, rendering stimulation with intermediate frequencies most efficient. Remarkably, we find that L/M-RR stimulation does not rely on a high spatial resolution, characterized by the density of stimulation sites in a target area, corresponding to a large M. In fact, L/M-RR stimulation with low resolution performs even better at low stimulation amplitudes. Our results provide computational evidence that L/M-RR stimulation may present a way to exploit modern segmented lead electrodes for long-lasting therapeutic effects.
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spelling pubmed-78931022021-02-20 Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation Khaledi-Nasab, Ali Kromer, Justus A. Tass, Peter A. Front Physiol Physiology Excessive neuronal synchrony is a hallmark of neurological disorders such as epilepsy and Parkinson's disease. An established treatment for medically refractory Parkinson's disease is high-frequency (HF) deep brain stimulation (DBS). However, symptoms return shortly after cessation of HF-DBS. Recently developed decoupling stimulation approaches, such as Random Reset (RR) stimulation, specifically target pathological connections to achieve long-lasting desynchronization. During RR stimulation, a temporally and spatially randomized stimulus pattern is administered. However, spatial randomization, as presented so far, may be difficult to realize in a DBS-like setup due to insufficient spatial resolution. Motivated by recently developed segmented DBS electrodes with multiple stimulation sites, we present a RR stimulation protocol that copes with the limited spatial resolution of currently available depth electrodes for DBS. Specifically, spatial randomization is realized by delivering stimuli simultaneously to L randomly selected stimulation sites out of a total of M stimulation sites, which will be called L/M-RR stimulation. We study decoupling by L/M-RR stimulation in networks of excitatory integrate-and-fire neurons with spike-timing dependent plasticity by means of theoretical and computational analysis. We find that L/M-RR stimulation yields parameter-robust decoupling and long-lasting desynchronization. Furthermore, our theory reveals that strong high-frequency stimulation is not suitable for inducing long-lasting desynchronization effects. As a consequence, low and high frequency L/M-RR stimulation affect synaptic weights in qualitatively different ways. Our simulations confirm these predictions and show that qualitative differences between low and high frequency L/M-RR stimulation are present across a wide range of stimulation parameters, rendering stimulation with intermediate frequencies most efficient. Remarkably, we find that L/M-RR stimulation does not rely on a high spatial resolution, characterized by the density of stimulation sites in a target area, corresponding to a large M. In fact, L/M-RR stimulation with low resolution performs even better at low stimulation amplitudes. Our results provide computational evidence that L/M-RR stimulation may present a way to exploit modern segmented lead electrodes for long-lasting therapeutic effects. Frontiers Media S.A. 2021-02-05 /pmc/articles/PMC7893102/ /pubmed/33613303 http://dx.doi.org/10.3389/fphys.2020.622620 Text en Copyright © 2021 Khaledi-Nasab, Kromer and Tass. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Khaledi-Nasab, Ali
Kromer, Justus A.
Tass, Peter A.
Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation
title Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation
title_full Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation
title_fullStr Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation
title_full_unstemmed Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation
title_short Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation
title_sort long-lasting desynchronization of plastic neural networks by random reset stimulation
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893102/
https://www.ncbi.nlm.nih.gov/pubmed/33613303
http://dx.doi.org/10.3389/fphys.2020.622620
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