Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.
Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.
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DOI：
10.3389/fnint.2012.00035
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发表时间：
2012
影响因子：
3.5
通讯作者：
Sarma SV
中科院分区：
文献类型：
--
作者：
Santaniello S;Montgomery EB Jr;Gale JT;Sarma SV
丘脑底核（subthalamic nucleus，DBS）的脑深部电刺激（Deep brain stimulation，DBS）直接调节基底神经节（basal ganglia，BG），但这种刺激如何影响上游的皮质在很大程度上是未知的。有证据表明，6-羟基多巴胺（OHDA）损伤的啮齿动物和促进运动诱发电位的帕金森病（PD）患者的皮质激活，但在正常与帕金森病的条件下，DBS设置对皮质活动的影响仍有争议。我们使用点过程模型来分析非稳态激活模式和两个非人灵长类动物的运动和感觉皮层的神经元间的依赖性在脑深部电刺激。这些特征在用1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）治疗后增强，其引起一致的PD样运动障碍，而高频（HF）DBS（即，≥100 Hz）均能显著降低MPTP治疗前后的短时波形（3-7 ms），并诱发短潜伏期的刺激后激活。低频DBS（即，≤50 Hz）对非平稳特征的影响可忽略不计。最后，通过使用信息理论的工具，受试者工作特征（ROC）曲线和信息率（IR）]，我们表明，这些模型的预测能力取决于DBS设置，即，皮层神经元的尖峰（spiking）的概率（其由点过程模型捕获）显著地取决于DBS输入的及时传递。这种依赖性随着DBS频率的增加而增加，并且对于高频DBS与低频DBS而言显著更大。总的来说，选择性抑制的非平稳功能和增加调制的尖峰概率表明，高频DBS增强运动和感觉皮层的神经元激活，大概是因为强化机制，这可能涉及反馈逆向和前馈顺向反应之间的重叠沿着BG-丘脑-皮层环路。
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated. We use point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of two non-human primates during STN DBS. These features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a consistent PD-like motor impairment, while high-frequency (HF) DBS (i.e., ≥100 Hz) strongly reduces the short-term patterns (period: 3–7 ms) both before and after MPTP treatment, and elicits a short-latency post-stimulus activation. Low-frequency DBS (i.e., ≤50 Hz), instead, has negligible effects on the non-stationary features. Finally, by using tools from the information theory [i.e., receiver operating characteristic (ROC) curve and information rate (IR)], we show that the predictive power of these models is dependent on the DBS settings, i.e., the probability of spiking of the cortical neurons (which is captured by the point process models) is significantly conditioned on the timely delivery of the DBS input. This dependency increases with the DBS frequency and is significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that HF STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the BG-thalamo-cortical loop.