Deep Brain Stimulation Reduces Tic-Related Neural Activity via Temporal Locking with Stimulus Pulses
Deep Brain Stimulation Reduces Tic-Related Neural Activity via Temporal Locking with Stimulus Pulses
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DOI：
10.1523/jneurosci.4874-12.2013
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发表时间：
2013-04-10
影响因子：
5.3
通讯作者：
Isoda, Masaki
中科院分区：
文献类型：
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作者：
McCairn, Kevin W.;Iriki, Atsushi;Isoda, Masaki
已显示出治疗基底神经节（BG）介导的运动性抽搐潜力的神经外科干预涉及靶向BG输出核（苍白球内侧（GPi））的高频脑深部电刺激（HF-DBS）。本研究使用了非人灵长类动物（Macaca fuscata）BG-冥想运动抽搐模型，并研究了可能构成GPi-HF-DBS有益作用的短期神经机制。在平行的行为抽搐的表达，神经元活动的阶段性变化出现在苍白球局灶性去抑制纹状体荷包牡丹碱。我们在GPi中输送HF-DBS，使得每30 s交替一次刺激和关闭刺激条件。肌电图（EMG）记录的分析表明，在刺激期间，抽搐相关的EMG振幅有显着减少。苍白球活动的分析表明，GPi-HF-DBS诱导持续和短暂的模式的兴奋和抑制在两个部分的GP。群体规模的放电率最初相对于基线升高，但在刺激停止时没有显著差异。行为和神经元放电率的调制与苍白球细胞中抽动相关的阶段性活动的减少有关。对短潜伏期反应的检查表明，放电率的变化与HF-DBS脉冲锁定细胞活性密切相关。这种时间锁定通常会引起单个细胞放电率的多相变化，这些变化在刺激期间动态变化。这些结果支持报告使用GPi-HF-DBS成功治疗运动性抽搐的临床研究，并证明GP内的潜在局部机制是通过刺激脉冲的时间锁定抑制抽搐相关活动。
A neurosurgical intervention that has shown potential for treating basal ganglia (BG) mediated motor tics involves high-frequency deep brain stimulation (HF-DBS) targeted to the output nucleus of the BG: the globus pallidus internus (GPi). This study used a nonhuman primate (Macaca fuscata) model of BG-meditated motor tics, and investigated the short-term neuronal mechanism that might underlie the beneficial effects of GPi-HF-DBS. In parallel with behavioral tic expressions, phasic alterations of neuronal activity emerged in the pallidum following focal disinhibition of the striatum with bicuculline. We delivered HF-DBS in the GPi in such a way that on-stimulation and off-stimulation conditions alternated every 30 s. Analysis of electromyographic (EMG) records showed that during on-stimulation, there were significant reductions in tic-related EMG amplitude. Analysis of pallidal activity showed that GPi-HF-DBS induced both sustained and transient patterns of excitation and inhibition in both segments of the GP. Population-scale firing rates were initially raised relative to baseline, but were not significantly different by the time stimulation ceased. Modulation of behavior and neuronal firing rates were associated with the reduction of tic-related phasic activity in pallidal cells. Examination of short-latency responses showed that firing rate changes were strongly associated with locking of the cells' activity with the HF-DBS pulse. This temporal locking often induced multiphasic changes of firing rates in individual cells, which dynamically changed across the stimulation period. These results support clinical studies that reported success in treating motor tics with GPi-HF-DBS, and demonstrate that the underlying local mechanism within the GP is suppression of tic-related activity through temporal locking with the stimulation pulse.