Donders Institute for Brain, Cognition and Behavior, Radboud University, 6500 HB Nijmegen, The Netherlands.
Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology and Parkinson Centre Nijmegen (ParC), 6500 HB Nijmegen, The Netherlands.
Brain. 2017 Mar 1;140(3):721-734. doi: 10.1093/brain/aww331.
Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor. From a sample of 40 patients with Parkinson's disease, we selected 15 patients with a clearly tremor-dominant phenotype. We compared tremor-related activity and effective connectivity (using combined electromyography-functional magnetic resonance imaging) on two occasions: ON and OFF dopaminergic medication. Building on a recently developed cerebral model of Parkinson's tremor, we tested the effect of dopamine on cerebral activity associated with the onset of tremor episodes (in the basal ganglia) and with tremor amplitude (in the cerebello-thalamo-cortical circuit). Dopaminergic medication reduced clinical resting tremor scores (mean 28%, range -12 to 68%). Furthermore, dopaminergic medication reduced tremor onset-related activity in the globus pallidus and tremor amplitude-related activity in the thalamic ventral intermediate nucleus. Network analyses using dynamic causal modelling showed that dopamine directly increased self-inhibition of the ventral intermediate nucleus, rather than indirectly influencing the cerebello-thalamo-cortical circuit through the basal ganglia. Crucially, the magnitude of thalamic self-inhibition predicted the clinical dopamine response of tremor. Dopamine reduces resting tremor by potentiating inhibitory mechanisms in a cerebellar nucleus of the thalamus (ventral intermediate nucleus). This suggests that altered dopaminergic projections to the cerebello-thalamo-cortical circuit have a role in Parkinson's tremor.aww331media15307619934001.
帕金森病静止性震颤与基底神经节和小脑-丘脑-皮质回路中的大脑活动改变有关。尽管帕金森病的特征是基底神经节中多巴胺的耗竭，但静止性震颤的多巴胺基础仍不清楚：多巴胺能药物可减少一些患者的震颤，但许多患者存在多巴胺抵抗性震颤。使用药理学功能磁共振成像，我们测试多巴胺干预如何影响帕金森震颤涉及的大脑回路。从 40 名帕金森病患者的样本中，我们选择了 15 名具有明显震颤优势表型的患者。我们在两种情况下比较了与震颤相关的活动和有效连接（使用肌电图-功能磁共振成像联合）：多巴胺能药物开启和关闭时。基于最近开发的帕金森震颤大脑模型，我们测试了多巴胺对与震颤发作起始（在基底神经节）和震颤幅度（在小脑-丘脑-皮质回路）相关的大脑活动的影响。多巴胺能药物可降低临床静止性震颤评分（平均降低 28%，范围-12 至 68%）。此外，多巴胺能药物可降低苍白球中与震颤起始相关的活动和丘脑腹侧中间核中与震颤幅度相关的活动。使用动态因果建模的网络分析表明，多巴胺直接增加了腹侧中间核的自抑制，而不是通过基底神经节间接影响小脑-丘脑-皮质回路。至关重要的是，丘脑的自抑制程度预测了震颤的临床多巴胺反应。多巴胺通过增强丘脑小脑核（腹侧中间核）的抑制机制来降低静止性震颤。这表明改变的多巴胺能投射到小脑-丘脑-皮质回路在帕金森震颤中起作用。
