Gao Lin-Lin, Zhang Jia-Rong, Chan Piu, Wu Tao
Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory on Parkinson's Disease, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing, China.
CNS Neurosci Ther. 2017 Jan;23(1):76-86. doi: 10.1111/cns.12634. Epub 2016 Sep 24.
To investigate the effects of levodopa on the basal ganglia motor circuit (BGMC) in Parkinson's disease (PD).
Thirty PD patients with asymmetrical bradykinesia and 30 control subjects were scanned using resting-state functional MRI. Functional connectivity of the BGMC was measured and compared before and after levodopa administration in patients with PD. The correlation between improvements in bradykinesia and changes in BGMC connectivity was examined.
In the PD-off state (before medication), the posterior putamen and internal globus pallidus (GPi) had decreased connectivity while the subthalamic nucleus (STN) had enhanced connectivity within the BGMC relative to control subjects. Levodopa administration increased the connectivity of posterior putamen- and GPi-related networks but decreased the connectivity of STN-related networks. Improvements in bradykinesia were correlated with enhanced connectivity of the posterior putamen-cortical motor pathway and with decreased connectivity of the STN-thalamo-cortical motor pathway.
In PD patients with asymmetrical bradykinesia, levodopa can partially normalize the connectivity of the BGMC with a larger effect on the more severely affected side. Moreover, the beneficial effect of levodopa on bradykinesia is associated with normalization of the striato-thalamo-cortical motor and STN-cortical motor pathways. Our findings inform the neural mechanism of levodopa treatment in PD.
研究左旋多巴对帕金森病(PD)基底神经节运动回路(BGMC)的影响。
对30例有不对称运动迟缓的PD患者和30名对照者进行静息态功能磁共振成像扫描。测量并比较PD患者服用左旋多巴前后BGMC的功能连接性。检查运动迟缓改善情况与BGMC连接性变化之间的相关性。
在帕金森病未服药状态(服药前),相对于对照者,壳核后部和苍白球内侧部(GPi)的连接性降低,而底丘脑核(STN)在BGMC内的连接性增强。服用左旋多巴增加了壳核后部和GPi相关网络的连接性,但降低了STN相关网络的连接性。运动迟缓的改善与壳核后部 - 皮质运动通路连接性增强以及STN - 丘脑 - 皮质运动通路连接性降低相关。
在有不对称运动迟缓的PD患者中,左旋多巴可部分使BGMC的连接性正常化,对受影响更严重的一侧影响更大。此外,左旋多巴对运动迟缓的有益作用与纹状体 - 丘脑 - 皮质运动和STN - 皮质运动通路的正常化有关。我们的研究结果揭示了左旋多巴治疗PD的神经机制。