Hwang Brian Y, Salimpour Yousef, Tsehay Yohannes K, Anderson William S, Mills Kelly A
Functional Neurosurgery Laboratory, Division of Functional Neurosurgery, Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Neuromodulation and Advanced Therapies Clinic, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Front Neurosci. 2020 Sep 29;14:558967. doi: 10.3389/fnins.2020.558967. eCollection 2020.
Deep brain stimulation (DBS) is an effective surgical therapy for Parkinson's disease (PD). However, limitations of the DBS systems have led to great interest in adaptive neuromodulation systems that can dynamically adjust stimulation parameters to meet concurrent therapeutic demand. Constant high-frequency motor cortex stimulation has not been remarkably efficacious, which has led to greater focus on modulation of subcortical targets. Understanding of the importance of timing in both cortical and subcortical stimulation has generated an interest in developing more refined, parsimonious stimulation techniques based on critical oscillatory activities of the brain. Concurrently, much effort has been put into identifying biomarkers of both parkinsonian and physiological patterns of neuronal activities to drive next generation of adaptive brain stimulation systems. One such biomarker is beta-gamma phase amplitude coupling (PAC) that is detected in the motor cortex. PAC is strongly correlated with parkinsonian specific motor signs and symptoms and respond to therapies in a dose-dependent manner. PAC may represent the overall state of the parkinsonian motor network and have less instantaneously dynamic fluctuation during movement. These findings raise the possibility of novel neuromodulation paradigms that are potentially less invasiveness than DBS. Successful application of PAC in neuromodulation may necessitate phase-dependent stimulation technique, which aims to deliver precisely timed stimulation pulses to a specific phase to predictably modulate to selectively modulate pathological network activities and behavior in real time. Overcoming current technical challenges can lead to deeper understanding of the parkinsonian pathophysiology and development of novel neuromodulatory therapies with potentially less side-effects and higher therapeutic efficacy.
深部脑刺激（DBS）是治疗帕金森病（PD）的一种有效手术疗法。然而，DBS系统的局限性引发了人们对自适应神经调节系统的极大兴趣，这种系统能够动态调整刺激参数以满足同时出现的治疗需求。持续高频运动皮层刺激效果并不显著，这使得人们更加关注对皮层下靶点的调节。对皮层和皮层下刺激中时间重要性的认识激发了人们开发基于大脑关键振荡活动的更精细、更简约刺激技术的兴趣。同时，人们投入了大量精力来识别帕金森病和神经元活动生理模式的生物标志物，以推动下一代自适应脑刺激系统的发展。其中一种生物标志物是在运动皮层中检测到的β-γ相位-幅度耦合（PAC）。PAC与帕金森病特异性运动体征和症状密切相关，并以剂量依赖方式对治疗产生反应。PAC可能代表帕金森病运动网络的整体状态，并且在运动过程中具有较小的瞬时动态波动。这些发现增加了新型神经调节范式的可能性，这些范式可能比DBS侵入性更小。PAC在神经调节中的成功应用可能需要相位依赖刺激技术，该技术旨在将精确计时的刺激脉冲传递到特定相位，以可预测地调节从而实时选择性地调节病理网络活动和行为。克服当前的技术挑战可以更深入地了解帕金森病的病理生理学，并开发出具有潜在更少副作用和更高治疗效果的新型神经调节疗法。
