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Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity

Several brain disorders are characterized by abnormal neuronal synchronization. To specifically counteract abnormal neuronal synchrony and, hence, related symptoms, coordinated reset (CR) stimulation was computationally developed. In principle, successive epochs of synchronizing and desynchronizing...

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Autores principales: Manos, Thanos, Diaz-Pier, Sandra, 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/PMC8455881/
https://www.ncbi.nlm.nih.gov/pubmed/34566681
http://dx.doi.org/10.3389/fphys.2021.716556
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author Manos, Thanos
Diaz-Pier, Sandra
Tass, Peter A.
author_facet Manos, Thanos
Diaz-Pier, Sandra
Tass, Peter A.
author_sort Manos, Thanos
collection PubMed
description Several brain disorders are characterized by abnormal neuronal synchronization. To specifically counteract abnormal neuronal synchrony and, hence, related symptoms, coordinated reset (CR) stimulation was computationally developed. In principle, successive epochs of synchronizing and desynchronizing stimulation may reversibly move neural networks with plastic synapses back and forth between stable regimes with synchronized and desynchronized firing. Computationally derived predictions have been verified in pre-clinical and clinical studies, paving the way for novel therapies. However, as yet, computational models were not able to reproduce the clinically observed increase of desynchronizing effects of regularly administered CR stimulation intermingled by long stimulation-free epochs. We show that this clinically important phenomenon can be computationally reproduced by taking into account structural plasticity (SP), a mechanism that deletes or generates synapses in order to homeostatically adapt the firing rates of neurons to a set point-like target firing rate in the course of days to months. If we assume that CR stimulation favorably reduces the target firing rate of SP, the desynchronizing effects of CR stimulation increase after long stimulation-free epochs, in accordance with clinically observed phenomena. Our study highlights the pivotal role of stimulation- and dosing-induced modulation of homeostatic set points in therapeutic processes.
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spelling pubmed-84558812021-09-23 Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity Manos, Thanos Diaz-Pier, Sandra Tass, Peter A. Front Physiol Physiology Several brain disorders are characterized by abnormal neuronal synchronization. To specifically counteract abnormal neuronal synchrony and, hence, related symptoms, coordinated reset (CR) stimulation was computationally developed. In principle, successive epochs of synchronizing and desynchronizing stimulation may reversibly move neural networks with plastic synapses back and forth between stable regimes with synchronized and desynchronized firing. Computationally derived predictions have been verified in pre-clinical and clinical studies, paving the way for novel therapies. However, as yet, computational models were not able to reproduce the clinically observed increase of desynchronizing effects of regularly administered CR stimulation intermingled by long stimulation-free epochs. We show that this clinically important phenomenon can be computationally reproduced by taking into account structural plasticity (SP), a mechanism that deletes or generates synapses in order to homeostatically adapt the firing rates of neurons to a set point-like target firing rate in the course of days to months. If we assume that CR stimulation favorably reduces the target firing rate of SP, the desynchronizing effects of CR stimulation increase after long stimulation-free epochs, in accordance with clinically observed phenomena. Our study highlights the pivotal role of stimulation- and dosing-induced modulation of homeostatic set points in therapeutic processes. Frontiers Media S.A. 2021-09-08 /pmc/articles/PMC8455881/ /pubmed/34566681 http://dx.doi.org/10.3389/fphys.2021.716556 Text en Copyright © 2021 Manos, Diaz-Pier and Tass. https://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
Manos, Thanos
Diaz-Pier, Sandra
Tass, Peter A.
Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity
title Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity
title_full Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity
title_fullStr Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity
title_full_unstemmed Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity
title_short Long-Term Desynchronization by Coordinated Reset Stimulation in a Neural Network Model With Synaptic and Structural Plasticity
title_sort long-term desynchronization by coordinated reset stimulation in a neural network model with synaptic and structural plasticity
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455881/
https://www.ncbi.nlm.nih.gov/pubmed/34566681
http://dx.doi.org/10.3389/fphys.2021.716556
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