Johnson Matthew D, Miocinovic Svjetlana, McIntyre Cameron C, Vitek Jerrold L
Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Neurotherapeutics. 2008 Apr;5(2):294-308. doi: 10.1016/j.nurt.2008.01.010.
Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.
慢性脑电刺激，即深部脑刺激（DBS），已成为药物难治性运动障碍的首选外科治疗方法。尽管DBS在临床上取得了显著成功，但其治疗机制仍未完全明确，这限制了提高治疗效果和简化刺激参数选择的机会。本综述探讨了理解DBS机制至关重要的三个问题。1）DBS如何影响有源电极附近的神经元组织？2）这些变化如何转化为对运动症状的治疗益处？3）这些效应如何依赖于特定的刺激部位？早期假说是刺激抑制了刺激部位的神经元活动，类似于切除手术的结果。最近的研究对这一观点提出了挑战，表明尽管DBS电极附近的躯体活动可能表现出显著的抑制或复杂的调制模式，但受刺激核的输出通过直接轴突兴奋跟随DBS脉冲序列。因此，固有活动被与刺激时间锁定且模式更规则的高频活动所取代。这些放电模式的变化被认为可以防止病理性爆发和振荡活动的传播，通过感觉运动信息的代偿性处理导致疾病症状减轻。尽管这一理论很有前景，但它并不能完全解释为什么DBS能在不同潜伏期改善运动症状。如果我们要充分发挥这一强大工具的潜力，在生理层面理解这些过程将至关重要。
