Pallidal Dysfunction Drives a Cerebellothalamic Circuit into Parkinson Tremor
Pallidal Dysfunction Drives a Cerebellothalamic Circuit into Parkinson Tremor
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DOI：
10.1002/ana.22361
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发表时间：
2011-02-01
影响因子：
11.2
通讯作者：
Toni, Ivan
中科院分区：
文献类型：
--
作者：
Helmich, Rick C.;Janssen, Marcel J. R.;Toni, Ivan
目的：帕金森病（PD）的特点是纹状体多巴胺耗竭，这可以解释运动迟缓和强直等临床症状，但不能解释静止性震颤。相反，静息性震颤与独特的小脑丘脑回路的活动增加有关。迄今为止，尚不清楚基底神经节和小脑丘脑回路之间的相互作用如何导致静息性震颤。方法：我们研究了 21 名震颤为主的 PD 患者、23 名非震颤性 PD 患者和 36 名对照者。使用功能磁共振成像，我们测量了基底节核（苍白球内部[GPi]、苍白球外部[GPe]、壳核、尾状核）和小脑丘脑回路之间的功能连接。在扫描过程中使用肌电图，我们测量了基底神经节和小脑丘脑回路中与震颤相关的活动。我们还使用碘-123-N-omega-氟丙基-2 β-甲氧甲氧基-3 β-(4-碘苯基)托烷 [[I-123]FP-CIT] 单光子发射计算机断层扫描定量纹状体苍白球多巴胺消耗。结果：苍白球（但不是纹状体）多巴胺消耗与临床震颤相关 严重程度。 GPi、GPe 和壳核在震颤发作时短暂激活，而小脑丘脑回路的活动随震颤幅度而波动。震颤为主的 PD 患者的 GPi 和壳核与小脑丘脑回路的功能连接增加，而小脑丘脑回路通过运动皮层降级。解释：静息性震颤可能是基底神经节和小脑丘脑回路之间病理性相互作用的结果。当接收来自多巴胺耗尽的基底神经节的瞬态信号时，控制震颤幅度的小脑丘脑回路似乎会被驱动产生震颤。这可以解释为什么尽管小脑丘脑回路会产生静息性震颤，但基底神经节功能障碍是发生静息性震颤所必需的。我们的模型还阐明了为什么针对基底神经节或小脑丘脑回路的神经外科干预措施都可以抑制震颤。安神经学 2011；69:269-281
Objective: Parkinson disease (PD) is characterized by striatal dopamine depletion, which explains clinical symptoms such as bradykinesia and rigidity, but not resting tremor. Instead, resting tremor is associated with increased activity in a distinct cerebellothalamic circuit. To date, it remains unknown how the interplay between basal ganglia and the cerebellothalamic circuit can result in resting tremor.Methods: We studied 21 tremor-dominant PD patients, 23 nontremor PD patients, and 36 controls. Using functional magnetic resonance imaging, we measured functional connectivity between basal ganglia nuclei (globus pallidus internus [GPi], globus pallidus externus [GPe], putamen, caudate) and the cerebellothalamic circuit. Using electromyography during scanning, we measured tremor-related activity in the basal ganglia and cerebellothalamic circuit. We also quantified striatopallidal dopamine depletion using iodine-123-N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane [[I-123]FP-CIT] single photon emission computed tomography.Results: Pallidal (but not striatal) dopamine depletion correlated with clinical tremor severity. The GPi, GPe, and putamen were transiently activated at the onset of tremor episodes, whereas activity in the cerebellothalamic circuit cofluctuated with tremor amplitude. The GPi and putamen of tremor-dominant PD patients had increased functional connectivity with the cerebellothalamic circuit, which was relegated through the motor cortex.Interpretation: Resting tremor may result from a pathological interaction between the basal ganglia and the cerebellothalamic circuit. The cerebellothalamic circuit, which controls tremor amplitude, appears to be driven into tremor generation when receiving transient signals from the dopamine-depleted basal ganglia. This may explain why basal ganglia dysfunction is required for developing resting tremor, although a cerebellothalamic circuit produces it. Our model also clarifies why neurosurgical interventions targeted at either the basal ganglia or the cerebellothalamic circuit can both suppress tremor. ANN NEUROL 2011;69:269-281