Neural diffusivity and pre-emptive epileptic seizure intervention.
Neural diffusivity and pre-emptive epileptic seizure intervention.
复制标题
DOI：
10.1371/journal.pcbi.1008448
复制
发表时间：
2020-12
影响因子：
4.3
通讯作者：
Richardson MP
中科院分区：
文献类型：
--
作者：
Fagerholm ED;Tangwiriyasakul C;Friston KJ;Violante IR;Williams S;Carmichael DW;Perani S;Turkheimer FE;Moran RJ;Leech R;Richardson MP
癫痫发作活动在大脑中的传播是一种广泛存在的病理生理学，原则上，它应该屈服于由神经元集合动力学数学模型指导的干预技术。在癫痫发作期间，神经活动将偏离其当前的动态制度，其中有一个显著的信号波动。神经活动的计算机治疗是理解健康大脑如何保持稳定以及病理如何导致癫痫发作的重要工具。希望是，包含在这些治疗的数学基础中，存在减轻不稳定性的潜在策略，例如通过外部刺激。在这里，我们证明了动态因果建模神经元状态方程推广到一个福克-普朗克的形式主义，如果一个扩展框架，以模拟的方式，活动传播沿着神经系统的结构连接。利用这个广义状态方程的雅可比矩阵，我们证明了一个初始不稳定的系统可以通过降低扩散系数而变得稳定。通过降低神经元波动向邻近区域扩散的速率。我们表明，对于易于癫痫发作的神经系统，这种扩散性的降低可以通过外部刺激来实现。具体来说，我们表明这种刺激应该以这样一种方式应用，即在其功能连接区域暂时反映病理区域的活动特征。这种反直觉的方法旨在先发制人地使用。为了减轻癫痫发作的影响，或者理想情况下，甚至从一开始就防止癫痫发作。我们利用从特发性全身性癫痫患者收集的功能性神经影像学数据进行模拟，提供原理证明，在这些数据中，我们成功地抑制了癫痫发作前不同子网络中的病理活动。我们希望这项技术能够成为未来实时监测和干预设备的基础，能够以非侵入性的方式治疗癫痫。癫痫是一种影响全世界5000多万人的疾病。目前的治疗方法包括危险的外科手术，切断大脑连接，甚至切除整个有问题的大脑区域。有药物可供选择，但只有约三分之一的患者有反应。然而，即使在这些情况下，药物也会引起严重的副作用，以至于患者有时会选择癫痫发作。我们正在提出一种创新的癫痫治疗方法，可以通过使用非侵入性电刺激来实现。具体来说，我们表明刺激应该以这样一种方式应用，即通过瞄准其邻近区域来反映问题大脑区域的活动。这种反直觉的方法是基于一个数学模型，在这个模型中，这种镜像策略被先发制人地应用，即早在癫痫发作有机会发生之前。希望未来的临床试验能够使用这种模型来减轻癫痫发作的影响，甚至从一开始就防止癫痫发作。
The propagation of epileptic seizure activity in the brain is a widespread pathophysiology that, in principle, should yield to intervention techniques guided by mathematical models of neuronal ensemble dynamics. During a seizure, neural activity will deviate from its current dynamical regime to one in which there are significant signal fluctuations. In silico treatments of neural activity are an important tool for the understanding of how the healthy brain can maintain stability, as well as of how pathology can lead to seizures. The hope is that, contained within the mathematical foundations of such treatments, there lie potential strategies for mitigating instabilities, e.g. via external stimulation. Here, we demonstrate that the dynamic causal modelling neuronal state equation generalises to a Fokker-Planck formalism if one extends the framework to model the ways in which activity propagates along the structural connections of neural systems. Using the Jacobian of this generalised state equation, we show that an initially unstable system can be rendered stable via a reduction in diffusivity–i.e., by lowering the rate at which neuronal fluctuations disperse to neighbouring regions. We show, for neural systems prone to epileptic seizures, that such a reduction in diffusivity can be achieved via external stimulation. Specifically, we show that this stimulation should be applied in such a way as to temporarily mirror the activity profile of a pathological region in its functionally connected areas. This counter-intuitive method is intended to be used pre-emptively–i.e., in order to mitigate the effects of the seizure, or ideally even prevent it from occurring in the first place. We offer proof of principle using simulations based on functional neuroimaging data collected from patients with idiopathic generalised epilepsy, in which we successfully suppress pathological activity in a distinct sub-network prior to seizure onset. Our hope is that this technique can form the basis for future real-time monitoring and intervention devices that are capable of treating epilepsy in a non-invasive manner. Epilepsy is a disease that affects over 50 million people worldwide. Current treatments include dangerous surgical procedures in which brain connections are severed, or even in which entire problem brain regions are removed. Pharmaceutical options are available, but only about one third of patients are responsive. However, even in these cases the drugs can cause such severe side effects that the patients sometimes choose to suffer seizures. We are proposing an innovative treatment of epilepsy that could be achieved by using non-invasive electrical stimulation. Specifically, we show that stimulation should be applied in such a way as to mirror the activity in a problem brain region, by targeting its neighbouring areas. This counterintuitive approach is based on a mathematical model in which this mirroring strategy is applied pre-emptively, i.e. long before the seizure has a chance to set in. The hope is that future clinical trials will be able to use this model to lessen the effect of seizures, or even prevent them from occurring in the first place.
登录
查看更多内容
影响因子：
3.4
作者：
Popovych OV;Tass PA
通讯作者：
Tass PA
影响因子：
5.6
作者：
Blumenfeld, H
通讯作者：
Blumenfeld, H
影响因子：
3.4
作者：
Glerean, Enrico;Salmi, Juha;Sams, Mikko
通讯作者：
Sams, Mikko
影响因子：
4.3
作者：
Deco, Gustavo;Jirsa, Viktor K.;Robinson, Peter A.;Breakspear, Michael;Friston, Karl J.
通讯作者：
Friston, Karl J.
影响因子：
4.6
作者：
Goodfellow M;Rummel C;Abela E;Richardson MP;Schindler K;Terry JR
通讯作者：
Terry JR