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

Frontiers in Physiology

Peter A. Tass¹  Thanos Manos³  Sandra Diaz-Pier⁵ 

[1] Data Lab Neuroscience, Institute for Advanced Simulation, Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH, JARA, Jülich, Germany;Institute of Neuroscience and Medicine, Brain and Behaviour (INM-7), Research Centre Jülich, Jülich, Germany;Laboratoire de Physique Théorique et Modélisation, CNRS, UMR 8089, CY Cergy Paris Université, Cergy-Pontoise Cedex, France;Medical Faculty, Institute of Systems Neuroscience, Heinrich Heine University Düsseldorf, Düsseldorf, Germany;;Simulation &

关键词: coordinated reset neuromodulation;    desynchronization;    spike time-dependent plasticity;    structural plasticity;    anti-kindling;   

DOI  :  10.3389/fphys.2021.716556

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown