Abstract:
Objective.Phase-amplitude coupling (PAC), the coupling of the amplitude of a faster brain rhythm to the phase of a slower brain rhythm, plays a significant role in brain activity and has been implicated in various neurological disorders. For example, in Parkinson\'s disease, PAC between the beta (13-30 Hz) and gamma (30-100 Hz) rhythms in the motor cortex is exaggerated, while in Alzheimer\'s disease, PAC between the theta (4-8 Hz) and gamma rhythms is diminished. Modulating PAC (i.e. reducing or enhancing PAC) using brain stimulation could therefore open new therapeutic avenues. However, while it has been previously reported that phase-locked stimulation can increase PAC, it is unclear what the optimal stimulation strategy to modulate PAC might be. Here, we provide a theoretical framework to narrow down the experimental optimisation of stimulation aimed at modulating PAC, which would otherwise rely on trial and error.Approach.We make analytical predictions using a Stuart-Landau model, and confirm these predictions in a more realistic model of coupled neural populations.Main results.Our framework specifies the critical Fourier coefficients of the stimulation waveform which should be tuned to optimally modulate PAC. Depending on the characteristics of the amplitude response curve of the fast population, these components may include the slow frequency, the fast frequency, combinations of these, as well as their harmonics. We also show that the optimal balance of energy between these Fourier components depends on the relative strength of the endogenous slow and fast rhythms, and that the alignment of fast components with the fast rhythm should change throughout the slow cycle. Furthermore, we identify the conditions requiring to phase-lock stimulation to the fast and/or slow rhythms.Significance.Together, our theoretical framework lays the foundation for guiding the development of innovative and more effective brain stimulation aimed at modulating PAC for therapeutic benefit.
摘要:
Objective.相位-振幅耦合(PAC),较快的脑节律的振幅与较慢的脑节律的相位的耦合,在大脑活动中起着重要作用,并与各种神经系统疾病有关。例如,在帕金森病中,运动皮层中β(13-30Hz)和γ(30-100Hz)节律之间的PAC被夸大了,而在老年痴呆症中,θ(4-8Hz)和伽马节律之间的PAC减小。因此,使用脑刺激调节PAC(即,减少或增强PAC)可以开辟新的治疗途径。然而,虽然以前有报道称锁相刺激可以增加PAC,目前尚不清楚调节PAC的最佳刺激策略可能是什么。这里,我们提供了一个理论框架来缩小旨在调节PAC的刺激的实验优化,否则将依赖于试验和错误。方法。我们使用斯图尔特-兰道模型进行分析预测,并在更现实的耦合神经群模型中证实这些预测。主要结果。我们的框架指定了刺激波形的关键傅立叶系数,应进行调整以最佳地调制PAC。根据快速群体的振幅响应曲线的特征,这些分量可能包括慢频率,快速的频率,这些组合,以及它们的谐波。我们还表明,这些傅立叶分量之间的最佳能量平衡取决于内源性缓慢和快速节律的相对强度,并且快速组件与快节奏的对齐应在整个慢速周期中发生变化。此外,我们确定需要将刺激锁相到快和/或慢节奏的条件。意义。一起,我们的理论框架为指导开发旨在调节PAC以获得治疗益处的创新且更有效的脑刺激奠定了基础.