Levodopa reinstates connectivity from prefrontal to premotor cortex during externally paced movement in Parkinson's disease
Levodopa reinstates connectivity from prefrontal to premotor cortex during externally paced movement in Parkinson's disease
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DOI：
10.1016/j.neuroimage.2013.11.023
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发表时间：
2014-04-15
期刊：
影响因子：
5.7
通讯作者：
Timmermann, Lars
中科院分区：
文献类型：
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作者：
Herz, Damian M.;Siebner, Hartwig R.;Timmermann, Lars
多巴胺缺乏影响分布神经区域活动的功能整合。有研究表明，多巴胺缺乏会导致前额叶和运动前区之间的神经相互作用中断，这可能是帕金森病患者运动控制受损的基础。在本研究中，我们用高密度脑电图记录了11例作为多巴胺缺乏症病理模型的PD患者和13例健康对照者的皮质活动。参与者以0.5 Hz的外部节奏重复右手食指的伸屈动作。这要求参与者将他们的运动速度与缓慢的外部速度保持一致。在多巴胺能药物停药至少12小时后（OFF状态）和多巴胺前体左旋多巴（ON状态）后（ON状态），研究患者分别在低水平和高水平多巴时前额叶和运动前区之间的振荡耦合。在10名患者和12名对照参与者中，多源波束形成分析发现，包括前额叶皮质（PFC）、外侧运动前皮质（lPM）、辅助运动区（SMA）和初级运动皮质（M1）在内的对侧皮质网络的任务相关激活。动态因果模型用于表征前额叶和运动前皮层区域之间的任务相关振荡耦合。健康参与者表现出从PFC到SMA的任务诱导耦合，该耦合在γ波段内被调制。在关闭状态下，PD患者在前额叶和前运动区之间没有表现出任何频率特异性的耦合。左旋多巴的应用恢复了PFC到SMA的任务相关耦合，这种耦合表现为高β - γ耦合。此外，从PFC到1PM，观察到强频内γ耦合以及交叉频率9-y耦合。使用左旋多巴后这种交叉频率0-y耦合的增强与个体运动功能的改善呈正相关。结果表明，多巴胺缺乏损害了在外部节奏运动任务中前额叶和运动前区域之间建立振荡耦合的能力。外源性多巴胺在PD患者中的应用恢复了生理前额叶-运动前区耦合，并诱导了从前额叶到运动前区的内频和交叉频耦合，这在健康参与者中是不表达的。C) 2013年作者。Elsevier Inn出版版权所有。
Dopamine deficiency affects functional integration of activity in distributed neural regions. It has been suggested that lack of dopamine induces disruption of neural interactions between prefrontal and premotor areas, which might underlie impairment of motor control observed in patients with Parkinson's disease (PD). In this study we recorded cortical activity with high-density electroencephalography in 11 patients with PD as a pathological model of dopamine deficiency, and 13 healthy control subjects. Participants performed repetitive extension-flexion movements of their right index finger, which were externally paced at a rate of 0.5 Hz. This required participants to align their movement velocity to the slow external pace. Patients were studied after at least 12-hour withdrawal of dopaminergic medication (OFF state) and after intake of the dopamine precursor levodopa (ON state) in order to examine oscillatory coupling between prefrontal and premotor areas during respectively low and high levels of dopamine. In 10 patients and 12 control participants multiple source beamformer analysis yielded task-related activation of a contralateral cortical network comprising prefrontal cortex (PFC), lateral premotor cortex (lPM), supplementary motor area (SMA) and primary motor cortex (M1). Dynamic causal modelling was used to characterize task-related oscillatory coupling between prefrontal and premotor cortical areas. Healthy participants showed task-induced coupling from PFC to SMA, which was modulated within the gamma-band. In the OFF state, PD patients did not express any frequency-specific coupling between prefrontal and premotor areas. Application of levodopa reinstated task-related coupling from PFC to SMA, which was expressed as high-beta-gamma coupling. Additionally, strong within-frequency gamma-coupling as well as cross-frequency 9-y coupling was observed from PFC to 1PM. Enhancement of this cross-frequency 0-y coupling after application of levodopa was positively correlated with individual improvement in motor function. The results demonstrate that dopamine deficiency impairs the ability to establish oscillatory coupling between prefrontal and premotor areas during an externally paced motor task. Application of extrinsic dopamine in PD patients reinstates physiological prefrontal-premotor coupling and additionally induces within- and cross-frequency coupling from prefrontal to premotor areas, which is not expressed in healthy participants. C) 2013 The Authors. Published by Elsevier Inn All rights reserved.