新型深部脑刺激模式的开发及研究进展

深部脑刺激(deep brain stimulation,DBS)已成为治疗帕金森病等运动障碍疾病的常规方法之一,并且在许多其他神经和精神疾病的治疗中也具有良好的应用前景.但是,目前常规DBS采用单通道恒定脉冲间隔的高频刺激(high frequency stimulation,HFS),刺激模式缺少多样化,限制了DBS在临床上的推广应用.为了开发更多DBS刺激模式,用于改善疗效、拓展应用范围、并节省刺激器的电能,近年来研究人员基于去同步调控机制,在脉冲序列的时间模式和空间排布两方面开发了DBS新模式.主要包括:变频序列(包括规则变频和随机变频)、不同空间位点上的多通道异步刺激以及变频和多通道两者的结合.这些新刺激模式能够提高DBS的临床疗效、降低刺激能耗,在帕金森病以及癫痫、强迫症和微意识障碍等其他脑疾病的治疗中都展现了良好的应用前景.更值得关注的是,多通道异步刺激不仅在刺激期间具有更好的即时疗效,而且刺激结束后还能长时间保持疗效,具有刺激后效应.这个特性突破了常规DBS主要为即时效应的局限性,展现了DBS新前景.本文在概述常规DBS模式及其去同步调控机制的基础上,综述变频脉冲刺激和多通道刺激等新型DBS模式,可以为促进DBS的发展提供有价值的信息.

Advances in The Development of New Stimulation Paradigms of Deep Brain Stimulation

Deep brain stimulation (DBS) has become one of the common treatments for movement disorders such as Parkinson''s disease. It is also a promising treatment for other neurological and psychiatric disorders. However, the stimulation paradigms of regular DBS are not diversified enough to meet the needs for extending its applications, because current DBS therapy usually utilizes single-channel high-frequency stimulation of electrical pulses with a constant inter-pulse-interval. According to the desynchronization mechanisms of DBS, new stimulation paradigms have been developed by designing the temporal and spatial patterns of pulse sequences to improve the therapeutic efficacy, to extend its application and to save the electric energy of impulse generator. The new paradigms include: stimulations of varying-frequency sequences (including regular varying-frequency and random varying-frequency), multi-channel asynchronous stimulations at different spatial locations, as well as the combined stimulations of varying-frequency and multi-channels. These new paradigms may improve the efficacy of DBS and reduce the energy consumption thereby showing good prospects in treating Parkinson''s disease and other brain diseases such as epilepsy, obsessive-compulsive and minimally conscious state. Notably, in addition to the better acute effect during the stimulations, the efficacy of multi-channel stimulations may last for a long time after the termination of stimulations, indicating a sustained effect or an after-effect. This performance breaks the limitation of regular DBS that has only acute effects and opens out a new prospect for DBS. Based on a summary of the stimulation paradigms of regular DBS and their underlying mechanisms, this review presents the development of new DBS paradigms on the stimulations of varying-frequency and multi-channels to generate asynchronous effects, thereby providing valuable information for the development of DBS.