High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model
High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model
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DOI：
10.1023/b:jcns.0000025686.47117.67
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发表时间：
2004-05-01
影响因子：
1.2
通讯作者：
Terman, D
中科院分区：
文献类型：
--
作者：
Rubin, JE;Terman, D
丘脑底核（subthalamic nucleus，DBS）或苍白球（globus pallidus，GPi）内段的脑深部电刺激（Deep brain stimulation，DBS）最近被认为是缓解帕金森病相关运动症状的重要干预形式，但其有效性机制尚不清楚。使用一个计算模型，本文认为DBS的工作原理是用紧张性高频放电代替病理性节律性基底神经节输出。在我们对帕金森病的模拟中，从GPi到丘脑的节律性抑制损害了丘脑皮层中继（TC）细胞对去极化输入（如感觉运动信号）的反应能力。高频刺激丘脑使GPi放电规律化，这恢复了TC的反应性，尽管导致对丘脑的GPi抑制的频率和幅度增加。我们提供了一个数学相平面分析的机制，确定TC中继功能在正常，帕金森病，DBS状态的简化模型。该分析突出了我们在这些不同条件下在TC细胞中观察到的低阈值钙T电流去失活的差异。替代方案涉及在皮层丘脑信号的收敛进行了讨论，并预测与这些结果，包括发生在某些TC细胞在帕金森氏症的状态和DBS的急剧减少的节律性反弹突发，陈述。这些结果证明了DBS如何通过增加靶细胞的放电率而不是关闭它们来工作。
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) has recently been recognized as an important form of intervention for alleviating motor symptoms associated with Parkinson's disease, but the mechanism underlying its effectiveness remains unknown. Using a computational model, this paper considers the hypothesis that DBS works by replacing pathologically rhythmic basal ganglia output with tonic, high frequency firing. In our simulations of parkinsonian conditions, rhythmic inhibition from GPi to the thalamus compromises the ability of thalamocortical relay (TC) cells to respond to depolarizing inputs, such as sensorimotor signals. High frequency stimulation of STN regularizes GPi firing, and this restores TC responsiveness, despite the increased frequency and amplitude of GPi inhibition to thalamus that result. We provide a mathematical phase plane analysis of the mechanisms that determine TC relay capabilities in normal, parkinsonian, and DBS states in a reduced model. This analysis highlights the differences in deinactivation of the low-threshold calcium T-current that we observe in TC cells in these different conditions. Alternative scenarios involving convergence of thalamic signals in the cortex are also discussed, and predictions associated with these results, including the occurrence of rhythmic rebound bursts in certain TC cells in parkinsonian states and their drastic reduction by DBS, are stated. These results demonstrate how DBS could work by increasing firing rates of target cells, rather than shutting them down.