Zeitler Magteld, Tass Peter A
Research Center Jülich, Institute for Neuroscience and Medicine, Brain and Behaviour (INM-7), Jülich, Germany.
Department of Neurosurgery, Stanford University, Stanford, CA, United States.
Front Physiol. 2018 May 8;9:512. doi: 10.3389/fphys.2018.00512. eCollection 2018.
A characteristic pattern of abnormal brain activity is abnormally strong neuronal synchronization, as found in several brain disorders, such as tinnitus, Parkinson's disease, and epilepsy. As observed in several diseases, different therapeutic interventions may induce a placebo effect that may be strong and hinder reliable clinical evaluations. Hence, to distinguish between specific, neuromodulation-induced effects and unspecific, placebo effects, it is important to mimic the therapeutic procedure as precisely as possibly, thereby providing controls that actually lack specific effects. Coordinated Reset (CR) stimulation has been developed to specifically counteract abnormally strong synchronization by desynchronization. CR is a spatio-temporally patterned multichannel stimulation which reduces the extent of coincident neuronal activity and aims at an anti-kindling, i.e., an unlearning of both synaptic connectivity and neuronal synchrony. Apart from acute desynchronizing effects, CR may cause sustained, long-lasting desynchronizing effects, as already demonstrated in pre-clinical and clinical proof of concept studies. In this computational study, we set out to computationally develop a sham stimulation protocol for multichannel desynchronizing stimulation. To this end, we compare acute effects and long-lasting effects of six different spatio-temporally patterned stimulation protocols, including three variants of CR, using a no-stimulation condition as additional control. This is to provide an inventory of different stimulation algorithms with similar fundamental stimulation parameters (e.g., mean stimulation rates) but qualitatively different acute and/or long-lasting effects. Stimulation protocols sharing basic parameters, but inducing nevertheless completely different or even no acute effects and/or after-effects, might serve as controls to validate the specific effects of particular desynchronizing protocols such as CR. In particular, based on our computational findings we propose a multichannel sham (i.e., inactive) stimulation protocol as control condition for phase 2 and phase 3 studies with desynchronizing multichannel stimulation techniques.
异常脑活动的一个特征模式是神经元同步异常强烈，这在多种脑部疾病中都有发现，如耳鸣、帕金森病和癫痫。正如在多种疾病中所观察到的，不同的治疗干预可能会诱发安慰剂效应，这种效应可能很强并阻碍可靠的临床评估。因此，为了区分特定的神经调节诱导效应和非特定的安慰剂效应，尽可能精确地模拟治疗程序很重要，从而提供实际上缺乏特定效应的对照。协调重置（CR）刺激已被开发出来，通过去同步化来特异性地对抗异常强烈的同步化。CR是一种时空模式化的多通道刺激，它减少了同步神经元活动的程度，旨在实现抗点燃，即消除突触连接性和神经元同步性。除了急性去同步化效应外，CR可能会引起持续的、长期的去同步化效应，这已在前临床和临床概念验证研究中得到证实。在这项计算研究中，我们着手通过计算开发一种用于多通道去同步化刺激的假刺激方案。为此，我们比较了六种不同时空模式化刺激方案的急性效应和长期效应，包括CR的三种变体，并将无刺激条件作为额外对照。这是为了提供一份不同刺激算法的清单，这些算法具有相似的基本刺激参数（如平均刺激率），但急性和/或长期效应在性质上有所不同。共享基本参数，但却诱发完全不同甚至没有急性效应和/或后效应的刺激方案，可能作为对照来验证特定去同步化方案（如CR）的特定效应。特别是，基于我们的计算结果，我们提出一种多通道假（即无效）刺激方案，作为使用多通道去同步化刺激技术进行二期和三期研究的对照条件。
