McCairn Kevin W, Turner Robert S
Department of Neurobiology, University of Pittsburgh, 4047 BST-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
J Neurophysiol. 2009 Apr;101(4):1941-60. doi: 10.1152/jn.91092.2008. Epub 2009 Jan 21.
Competing theories seek to account for the therapeutic effects of high-frequency deep brain stimulation (DBS) of the internal globus pallidus (GPi) for medically intractable Parkinson's disease. To investigate this question, we studied the spontaneous activity of 102 pallidal neurons during GPiDBS in two macaques rendered parkinsonian by administration of MPTP. Stimulation through macroelectrodes in the GPi (> or =200 microA at 150 Hz for 30 s) reduced rigidity in one animal and increased spontaneous movement in both. Novel artifact subtraction methods allowed uninterrupted single-unit recording during stimulation. GPiDBS induced phasic (78% of cells) or sustained (22%) peristimulus changes in firing in both pallidal segments. A subset of cells responded at short latency (<2 ms) in a manner consistent with antidromic driving. Later phasic increases clustered at 3- to 5-ms latency. Stimulation-induced decreases were either phasic, clustered at 1-3 ms, or sustained, showing no peristimulus modulation. Response latency and magnitude often evolved over 30 s of stimulation, but responses were relatively stable by the end of that time. GPiDBS reduced mean firing rates modestly and only in GPi (-6.9 spikes/s). Surprisingly, GPiDBS had no net effect on the prevalence or structure of burst firing. GPiDBS did reduce the prevalence of synchronized low-frequency oscillations. Some cell pairs became synchronized instead at the frequency of stimulation. Suppression of low-frequency oscillations did not require high-frequency synchronization, however, or even the presence of a significant peristimulus response. In summary, the therapeutic effects of GPiDBS may be mediated by an abolition of low-frequency synchronized oscillations as a result of phasic driving.
相互竞争的理论试图解释内侧苍白球（GPi）高频深部脑刺激（DBS）对药物难治性帕金森病的治疗效果。为了研究这个问题，我们在两只通过注射MPTP而患帕金森病的猕猴进行GPi DBS期间，研究了102个苍白球神经元的自发活动。通过GPi中的宏观电极进行刺激（150 Hz时≥200 μA，持续30秒），在一只动物中降低了僵硬程度，在两只动物中均增加了自发运动。新颖的伪迹减法方法允许在刺激期间进行不间断的单单元记录。GPi DBS在两个苍白球节段中均诱发了刺激期间放电的相位性（78%的细胞）或持续性（22%）变化。一部分细胞以与逆向驱动一致的方式在短潜伏期（<2毫秒）做出反应。后期的相位性增加集中在3至5毫秒的潜伏期。刺激诱发的减少要么是相位性的，集中在1至3毫秒，要么是持续性的，未显示刺激期间的调制。反应潜伏期和幅度通常在30秒的刺激过程中演变，但在该时间段结束时反应相对稳定。GPi DBS适度降低了平均放电率，且仅在GPi中降低（-6.9个脉冲/秒）。令人惊讶的是，GPi DBS对爆发性放电的发生率或结构没有净影响。GPi DBS确实降低了同步低频振荡的发生率。然而，一些细胞对反而在刺激频率下变得同步。抑制低频振荡不需要高频同步，甚至不需要显著的刺激期间反应。总之，GPi DBS的治疗效果可能是由于相位性驱动导致低频同步振荡的消除所介导的。
