Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype
Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype
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DOI：
10.1212/01.wnl.0000338699.56379.11
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发表时间：
2009-03-24
期刊：
影响因子：
9.9
通讯作者：
Siebner, H. R.
中科院分区：
文献类型：
--
作者：
van Nuenen, B. F. L.;Weiss, M. M.;Siebner, H. R.
目的：使用神经发生-神经影像相结合的方法来检查人类运动系统中临床前多巴胺能黑质纹状体功能障碍的功能后果。具体来说，我们研究了与隐性遗传性帕金森病相关的不同基因中的单一杂合突变如何改变连续手指运动的皮层控制。方法：使用功能性 MRI (fMRI) 对携带单一杂合 Parkin (n = 13) 或 PINK1 (n = 9) 突变的非表现个体和没有这些突变的 23 名健康对照进行研究。在功能磁共振成像期间，参与者用右手惯用手执行三个简单的拇指到手指相对运动序列。由于 Parkin 和 PINK1 杂合突变会导致潜在的多巴胺能黑质纹状体功能障碍，因此我们预测通常参与复杂运动序列控制的吻侧前运动区会出现补偿性募集。我们预计这种过度活动与潜在的基因型无关。结果：所有组的任务表现都是可比的。简单运动序列任务的执行始终激活突变携带者的吻侧辅助运动区和右吻侧背侧前运动皮层，但在对照组中则不然。这些前运动区的任务相关激活在 Parkin 或 PINK1 突变携带者中是相似的。结论：与隐性遗传性帕金森病相关的不同基因的突变与在简单的运动序列任务中嘴侧辅助运动区和嘴侧背侧前运动皮层的额外募集相关。这些运动前区的招募与潜在的基因型无关。观察到的激活很可能反映了在轻度多巴胺能缺陷的情况下维持运动功能的“通用”补偿机制。神经病学（R）2009； 72：1041-1047
Objective: To use a combined neurogenetic-neuroimaging approach to examine the functional consequences of preclinical dopaminergic nigrostriatal dysfunction in the human motor system. Specifically, we examined how a single heterozygous mutation in different genes associated with recessively inherited Parkinson disease alters the cortical control of sequential finger movements.Methods: Nonmanifesting individuals carrying a single heterozygous Parkin (n = 13) or PINK1 (n = 9) mutation and 23 healthy controls without these mutations were studied with functional MRI (fMRI). During fMRI, participants performed simple sequences of three thumb-to-finger opposition movements with their right dominant hand. Since heterozygous Parkin and PINK1 mutations cause a latent dopaminergic nigrostriatal dysfunction, we predicted a compensatory recruitment of those rostral premotor areas that are normally implicated in the control of complex motor sequences. We expected this overactivity to be independent of the underlying genotype.Results: Task performance was comparable for all groups. The performance of a simple motor sequence task consistently activated the rostral supplementary motor area and right rostral dorsal premotor cortex in mutation carriers but not in controls. Task-related activation of these premotor areas was similar in carriers of a Parkin or PINK1 mutation.Conclusion: Mutations in different genes linked to recessively inherited Parkinson disease are associated with an additional recruitment of rostral supplementary motor area and rostral dorsal premotor cortex during a simple motor sequence task. These premotor areas were recruited independently of the underlying genotype. The observed activation most likely reflects a "generic" compensatory mechanism to maintain motor function in the context of a mild dopaminergic deficit. Neurology (R) 2009; 72: 1041-1047