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基底神经节的变化模式:多巴胺能驱动减少下的运动切换。

Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive.

机构信息

Wellcome Trust Centre for Neuroimaging, University College London, 12 Queen Square, London WC1N 3BG, United Kingdom.

Centre for BrainHealth, Univesity of Texas at Dallas, 2200 West Mockingbird Lane, Dallas, TX 75235, USA.

出版信息

Sci Rep. 2016 Mar 23;6:23327. doi: 10.1038/srep23327.

Abstract

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.

摘要

基底神经节中的动作选择通常在标准模型的框架内进行描述,将低多巴胺能驱动与运动抑制联系起来。虽然这个模型很强大,但它并不能解释一些临床和实验数据,包括运动障碍的治疗效果各不相同。我们在接受丘脑底核深部脑刺激(DBS)治疗的帕金森病患者中测试了这个模型的预测,重点是对不断变化的环境进行适应性感觉运动反应以及在动作不再合适时保持动作。令人惊讶的是,我们观察到在刺激下的坚持时间延长,并且在比较两种情况时,在执行的运动选择方面存在个体间的高度可变性。为了解释这些数据,我们修改了标准模型,探索了其参数空间及其相关的运动功能,并发现,根据苍白球外部和内部部分之间的有效连通性以及感觉输入的显著性,低多巴胺能驱动可能导致过度的、功能失调的运动切换,而不仅仅是运动抑制。这个新的框架提供了对 DBS 背后的生物物理机制的深入了解,允许根据间接通路中信号与基线比率的变化来描述,与标准模型相比,它更好地解释了已知的电生理数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/097d/4804216/cd26c82df7a1/srep23327-f1.jpg

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