Dopaminergic modulation of motor network dynamics in Parkinson's disease.
Dopaminergic modulation of motor network dynamics in Parkinson's disease.
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DOI：
10.1093/brain/awu381
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Grefkes C
中科院分区：
文献类型：
--
作者：
Michely J;Volz LJ;Barbe MT;Hoffstaedter F;Viswanathan S;Timmermann L;Eickhoff SB;Fink GR;Grefkes C
Michely等人使用基于功能性MRI的连接性分析，研究了帕金森病运动控制中涉及的神经网络动力学的多巴胺能调制。这些发现为运动迟缓和执行功能缺陷的病理生理学提供了见解，并有助于解释为什么多巴胺能治疗对前者有更大的影响。虽然帕金森病的特征性运动症状，如运动迟缓，通常在多巴胺能药物治疗下得到改善，但高级运动控制的缺陷反应较低。我们在这里研究了多巴胺能调制的网络动力学基础的基本运动性能，即手指轻敲，和更高的电机控制，即内部和外部线索的运动准备和选择。12名患者，评估ON和OFF药物，和12名年龄匹配的健康受试者进行功能磁共振成像。动态因果模型被用来评估有效的连接在运动网络，包括皮层和皮层下区域。特别是，我们研究了基础和高级运动控制的损伤以及多巴胺能治疗诱导的效应是否是由于以下方面的连接变化：（i）包括补充运动区的近中运动前环;（ii）包括外侧运动前皮质的外侧运动前环;以及（iii）皮质-皮质下相互作用。在行为水平上，我们观察到一个显着放缓的运动准备和选择时，患者的内部，而不是外部线索。在外部提示过程中保持的表现与前额叶皮层和外侧运动前皮层OFF药物之间的连接增强相关，与多巴胺能减退状态下外侧运动前区环路的上下文依赖性代偿作用相容。多巴胺能药物显著改善患者的手指敲击速度，这与药物诱导的前额叶皮层与辅助运动区（即近中前运动环路）的耦合增加相关。此外，只有在手指轻敲条件下，药物治疗的患者表现出增强的兴奋性影响施加的皮质运动前区和丘脑后壳核。总之，多巴胺能药物对运动迟缓的改善似乎是由近中运动前环和皮质-纹状体相互作用内的连接增强所驱动的。相比之下，药物并没有改善内部运动控制缺陷，同时在连接水平上失去了效果。多巴胺能药物对运动控制网络动力学的这种差异性作用为临床发现提供了新的见解，即在帕金森病中，多巴胺能药物特别影响运动迟缓，但对执行功能的影响较小。
Using connectivity analyses based on functional MRI, Michely et al. investigate dopaminergic modulation of neural network dynamics involved in motor control in Parkinson’s disease. The findings provide insights into the pathophysiology underlying bradykinesia and deficits in executive function, and help to explain why dopaminergic treatments have a greater effect on the former. Although characteristic motor symptoms of Parkinson’s disease such as bradykinesia typically improve under dopaminergic medication, deficits in higher motor control are less responsive. We here investigated the dopaminergic modulation of network dynamics underlying basic motor performance, i.e. finger tapping, and higher motor control, i.e. internally and externally cued movement preparation and selection. Twelve patients, assessed ON and OFF medication, and 12 age-matched healthy subjects underwent functional magnetic resonance imaging. Dynamic causal modelling was used to assess effective connectivity in a motor network comprising cortical and subcortical regions. In particular, we investigated whether impairments in basic and higher motor control, and the effects induced by dopaminergic treatment are due to connectivity changes in (i) the mesial premotor loop comprising the supplementary motor area; (ii) the lateral premotor loop comprising lateral premotor cortex; and (iii) cortico-subcortical interactions. At the behavioural level, we observed a marked slowing of movement preparation and selection when patients were internally as opposed to externally cued. Preserved performance during external cueing was associated with enhanced connectivity between prefrontal cortex and lateral premotor cortex OFF medication, compatible with a context-dependent compensatory role of the lateral premotor loop in the hypodopaminergic state. Dopaminergic medication significantly improved finger tapping speed in patients, which correlated with a drug-induced coupling increase of prefrontal cortex with the supplementary motor area, i.e. the mesial premotor loop. In addition, only in the finger tapping condition, patients ON medication showed enhanced excitatory influences exerted by cortical premotor regions and the thalamus upon the putamen. In conclusion, the amelioration of bradykinesia by dopaminergic medication seems to be driven by enhanced connectivity within the mesial premotor loop and cortico-striatal interactions. In contrast, medication did not improve internal motor control deficits concurrent to missing effects at the connectivity level. This differential effect of dopaminergic medication on the network dynamics underlying motor control provides new insights into the clinical finding that in Parkinson’s disease dopaminergic drugs especially impact on bradykinesia but less on executive functions.
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影响因子：
11.2
作者：
Godefroy, Olivier;Azouvi, Philippe;Meulemans, Thierry
通讯作者：
Meulemans, Thierry
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
14.5
作者：
Esposito, Fabrizio;Tessitore, Alessandro;Tedeschi, Gioacchino
通讯作者：
Tedeschi, Gioacchino
影响因子：
8.6
作者：
Farid, Karim;Sibon, Igor;Allard, Michele
通讯作者：
Allard, Michele
影响因子：
5.7
作者：
Grefkes, Christian;Eickhoff, Simon B.;Fink, Gereon R.
通讯作者：
Fink, Gereon R.