Department of Neurology, University of Lübeck, Lübeck, Germany; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Department of Neurology, University of Lübeck, Lübeck, Germany; Department of Internal Medicine, University of Lübeck, Lübeck, Germany.
Parkinsonism Relat Disord. 2019 Oct;67:99-104. doi: 10.1016/j.parkreldis.2019.09.003. Epub 2019 Sep 3.
In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) go beyond DRT effects including highly beneficial tremor suppression.
Here, we aimed to determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN DBS.
In a repeated-measurement design, 26 medicated PD patients (60.9 years (SD 8.9)) were investigated using resting state fMRI while bipolar STN stimulation was (i) active or (ii) switched off, and dynamic causal modelling was subsequently performed.
DBS improved the MDS-UPDRS-III score by 26.4% (DBS ON/Med ON vs. DBS OFF/Med ON). Active stimulation resulted in an increased effective connectivity from cerebellum to putamen (p = 0.00118). In addition, there was a stronger coupling from PFC to cerebellum (p = 0.021), as well as from cerebellum to SMA (p = 0.043) on an uncorrected level. Coupling strength from PFC to cerebellum correlated with the DBS-related change of the resting tremor subscore (r = 0.54, p = 0.031). Self-connections increased as a function of DBS in the right PFC, PMC, SMA, M1, thalamus and left cerebellum.
DBS-related improvement of Parkinsonian signs appears to be driven by an interaction between the cerebellum and the putamen. Resting tremor suppression may be related to an enhanced prefronto-cerebellar network. Activation of the mesial premotor loop (PFC-SMA) as seen in DRT may thus be secondary due to the primary modulation of cerebellar networks.
在帕金森病（PD）中，多巴胺替代疗法（DRT）增强了前额叶皮层（PFC）和辅助运动区（SMA）的有效连接。丘脑底核（STN）深部脑刺激（DBS）的临床效果超出了 DRT 效应，包括高度有益的震颤抑制。
本研究旨在通过慢性 STN-DBS 的 PD 患者的静息状态 fMRI 确定与 DBS 相关的运动网络变化。
在重复测量设计中，研究人员使用静息状态 fMRI 对 26 名接受药物治疗的 PD 患者（60.9 岁（SD 8.9））进行了调查，同时双极 STN 刺激处于（i）活动状态或（ii）关闭状态，随后进行了动态因果建模。
DBS 将 MDS-UPDRS-III 评分提高了 26.4%（DBS ON/Med ON 与 DBS OFF/Med ON）。主动刺激导致小脑到壳核的有效连接增加（p=0.00118）。此外，在未校正的水平上，PFC 与小脑之间的耦合更强（p=0.021），以及小脑与 SMA 之间的耦合更强（p=0.043）。PFC 与小脑的耦合强度与 DBS 相关的静息震颤亚评分变化相关（r=0.54，p=0.031）。右侧 PFC、PMC、SMA、M1、丘脑和左侧小脑的自连接随 DBS 而增加。
帕金森病症状的 DBS 相关改善似乎是由小脑和壳核之间的相互作用驱动的。静息震颤抑制可能与增强的前额叶-小脑网络有关。因此，DRT 中看到的内侧运动前环（PFC-SMA）的激活可能是由于小脑网络的主要调制而继发的。
