How stimulation frequency and intensity impact on the long-lasting effects of coordinated reset stimulation.
How stimulation frequency and intensity impact on the long-lasting effects of coordinated reset stimulation.
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DOI：
10.1371/journal.pcbi.1006113
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发表时间：
2018-05
影响因子：
4.3
通讯作者：
Tass PA
中科院分区：
文献类型：
--
作者：
Manos T;Zeitler M;Tass PA
几种脑部疾病的特征在于异常强的神经元同步性。协调复位（CR）刺激的计算设计，以专门抵消异常的神经元同步化过程的去同步化。在尖峰定时依赖性可塑性（STDP）的存在下，这可能导致突触兴奋性权重的降低，并最终导致抗点燃，即对异常突触连接和异常神经元同步性的遗忘。在临床前和临床概念验证研究中，已验证了CR刺激的持久去凝血作用。然而，目前尚不清楚如何最佳地选择CR刺激频率，即递送CR刺激的重复率。这项工作提出了第一个计算研究的依赖性的急性和长期的结果上的CR刺激频率在神经网络与STDP。为此，在广泛的刺激频率和强度范围内，使用快速变化序列（RVS）以及缓慢变化序列（SVS）进行CR刺激。我们的研究结果表明，急性去极化，在刺激过程中实现，并不一定会导致长期去极化后停止刺激。通过比较两种不同CR方案的长期效果，RVS CR刺激对刺激频率的变化更稳健。而刺激SVS CR可获得较强的抗点燃效应。我们揭示了有利于长期去磁化的特定参数范围。例如，在弱强度下并且刺激频率在神经元放电率范围内的RVS CR刺激被证明是有效和稳健的，特别是如果刺激参数的闭环适配（技术上）不可用的话。从临床角度来看，这可能与侵入性和非侵入性CR刺激相关。异常强烈的神经元同步被发现在一些大脑疾病。为了特异性地抵消异常神经元同步性，并因此抵消相关症状，开发了协调复位（CR）刺激。CR刺激采用神经系统的基本可塑性和动态自组织原理。其基本目标是诱导持续停止刺激的持久去兴奋作用。后者是减少侵入性治疗（如脑深部电刺激）副作用的关键。此外，持续的刺激效果为非侵入性神经调节治疗铺平了道路，其中定期或偶尔递送几个小时的刺激可以提供实质性的缓解。在几项临床前和临床研究中，已证实了CR诱导的长效降血脂治疗效果。然而，我们在这里提出了第一个计算研究，系统地调查刺激结果的关键刺激参数的影响。我们的研究结果提供了实验可检验的预测，临床前和临床研究相关。此外，我们的研究结果可能有助于刺激技术，使探测一般的脑节律的功能作用。
Several brain diseases are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was computationally designed to specifically counteract abnormal neuronal synchronization processes by desynchronization. In the presence of spike-timing-dependent plasticity (STDP) this may lead to a decrease of synaptic excitatory weights and ultimately to an anti-kindling, i.e. unlearning of abnormal synaptic connectivity and abnormal neuronal synchrony. The long-lasting desynchronizing impact of CR stimulation has been verified in pre-clinical and clinical proof of concept studies. However, as yet it is unclear how to optimally choose the CR stimulation frequency, i.e. the repetition rate at which the CR stimuli are delivered. This work presents the first computational study on the dependence of the acute and long-term outcome on the CR stimulation frequency in neuronal networks with STDP. For this purpose, CR stimulation was applied with Rapidly Varying Sequences (RVS) as well as with Slowly Varying Sequences (SVS) in a wide range of stimulation frequencies and intensities. Our findings demonstrate that acute desynchronization, achieved during stimulation, does not necessarily lead to long-term desynchronization after cessation of stimulation. By comparing the long-term effects of the two different CR protocols, the RVS CR stimulation turned out to be more robust against variations of the stimulation frequency. However, SVS CR stimulation can obtain stronger anti-kindling effects. We revealed specific parameter ranges that are favorable for long-term desynchronization. For instance, RVS CR stimulation at weak intensities and with stimulation frequencies in the range of the neuronal firing rates turned out to be effective and robust, in particular, if no closed loop adaptation of stimulation parameters is (technically) available. From a clinical standpoint, this may be relevant in the context of both invasive as well as non-invasive CR stimulation. Abnormally strong neuronal synchronization is found in a number of brain disorders. To specifically counteract abnormal neuronal synchrony and, hence, related symptoms, Coordinated Reset (CR) stimulation was developed. CR stimulation employs basic plasticity and dynamic self-organization principles of the nervous system. Its fundamental goal is to induce long-lasting desynchronizing effects that persist cessation of stimulation. The latter are key to reducing side effects of invasive therapies such as deep brain stimulation. Furthermore, sustained stimulation effects pave the way for non-invasive neuromodulation treatments, where a few hours of stimulation delivered regularly or occasionally may provide substantial relief. Long-lasting CR-induced desynchronizing therapeutic effects have been verified in several pre-clinical and clinical studies. However, we here present the first computational study that systematically investigates the impact of key stimulation parameters on the stimulation outcome. Our results provide experimentally testable predictions that are relevant for pre-clinical and clinical studies. Furthermore, our results may contribute to stimulation techniques that enable to probe the functional role of brain rhythms in general.
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DOI：
10.1177/1073858409354384
发表时间：
2011-02
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Deco G;Corbetta M
通讯作者：
Corbetta M
影响因子：
8.6
作者：
Arguello, C. J.;Rosenthal, E. P.;Pasupathy, A. N.
通讯作者：
Pasupathy, A. N.
影响因子：
9.9
作者：
Contarino, M. Fiorella;Bour, Lo J.;Schuurman, P. R.
通讯作者：
Schuurman, P. R.
影响因子：
5.6
作者：
da Silva, FL;Blanes, W;Velis, DN
通讯作者：
Velis, DN
影响因子：
8.6
作者：
Belykh, I;de Lange, E;Hasler, M
通讯作者：
Hasler, M