Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive.
Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive.
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DOI：
10.1038/srep23327
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发表时间：
2016-03-23
影响因子：
4.6
通讯作者：
Dolan RJ
中科院分区：
文献类型：
--
作者：
Fiore VG;Rigoli F;Stenner MP;Zaehle T;Hirth F;Heinze HJ;Dolan RJ
基底神经节中的动作选择通常在标准模型的框架内描述，将低多巴胺能驱动与运动抑制相关联。虽然这个模型很强大，但它不能解释几个临床和实验数据，包括不同运动障碍的治疗效果。我们在帕金森病患者中测试了该模型的预测，开启和关闭丘脑底脑深部电刺激（DBS），重点是对不断变化的环境的适应性感觉运动反应和维持动作，直到它不再适合。令人惊讶的是，我们观察到长期的毅力下的刺激，和高个体间的变异性进行比较时，两种条件下的电机选择。为了解释这些数据，我们修改了标准模型，探索其参数空间和相关的运动功能，并发现，根据苍白球外部和内部部分之间的有效连接和感觉输入的显着性，低多巴胺能驱动可以导致增加，功能障碍，运动开关，除了运动抑制。这种新的框架提供了深入了解DBS的生物物理机制，允许在间接途径中的信号与基线比的改变方面进行描述，与标准模型相比，这更好地解释了已知的电生理数据。
Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model.