Department of Mathematical Sciences and Center for Mathematical Biosciences, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States of America.
PLoS One. 2012;7(7):e41598. doi: 10.1371/journal.pone.0041598. Epub 2012 Jul 27.
The exact origin of tremor in Parkinson's disease remains unknown. We explain why the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor generator and consider a conductance-based model of subthalamo-pallidal circuits embedded into a simplified representation of the basal ganglia-thalamo-cortical circuit to investigate the dynamics of this loop. We show how variation of the strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical loop (representing the decreasing dopamine level in Parkinson's disease) leads to the occurrence of tremor-like burst firing. These tremor-like oscillations are suppressed when the connections are modulated back to represent a higher dopamine level (as it would be the case in dopaminergic therapy), as well as when the basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative anti-parkinsonian surgeries). Thus, the proposed model provides an explanation for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The strengthening of the loop leads to tremor oscillations, while the weakening or disconnection of the loop suppresses them. The loop origin of parkinsonian tremor also suggests that new tremor-suppression therapies may have anatomical targets in different cortical and subcortical areas as long as they are within the basal ganglia-thalamo-cortical loop.
帕金森病震颤的确切起源仍不清楚。我们解释了为什么现有数据集中在基底神经节-丘脑-皮质回路作为震颤发生器，并且考虑了一个基于电导率的亚丘脑-苍白球电路模型，该模型嵌入到简化的基底神经节-丘脑-皮质回路中，以研究该回路的动力学。我们展示了基底神经节-丘脑-皮质回路中多巴胺调制连接强度的变化（代表帕金森病中多巴胺水平的降低）如何导致类似震颤的爆发性放电的发生。当连接被调制回代表更高的多巴胺水平（如在多巴胺能治疗中那样）时，以及当基底神经节-丘脑-皮质回路被阻断（如在消融性抗帕金森手术中那样）时，这些类似震颤的振荡会被抑制。因此，所提出的模型为基底神经节-丘脑-皮质回路的震颤产生机制提供了一个解释。环路的增强导致震颤振荡，而环路的减弱或断开抑制它们。帕金森震颤的环路起源也表明，新的震颤抑制疗法可能有解剖学靶点，位于不同的皮质和皮质下区域，只要它们在基底神经节-丘脑-皮质回路内。
