Motor reorganization in asymptomatic carriers of a single mutant Parkin allele:: a human model for presymptomatic parkinsonism
Motor reorganization in asymptomatic carriers of a single mutant Parkin allele:: a human model for presymptomatic parkinsonism
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DOI：
10.1093/brain/awh572
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发表时间：
2005-10-01
期刊：
影响因子：
14.5
通讯作者：
Siebner, HR
中科院分区：
文献类型：
--
作者：
Buhmann, C;Binkofski, F;Siebner, HR
帕金森氏基因突变是最常见的已知早发性帕金森氏症的单一原因。有研究表明，无症状的携带单一突变等位基因的人在纹状体中有潜在的突触前多巴胺能功能障碍。在这里，我们使用功能性MRI来绘制12名无症状的帕金突变携带者和12名健康的非携带者在内部选择或外部决定的手指运动中与运动相关的神经元活动。内部选择运动组的平均反应时间比外部引导运动组短63 ms （P = 0.003）。两组平均反应时间差异无统计学意义（P < 0.05）。与外部决定的运动相比，内部选择运动导致吻侧运动区域的激活更强，包括吻侧扣带运动区（rCMA）、吻侧辅助运动区、内侧和背外侧前额皮质。基因型对运动相关的激活模式有显著影响。无症状携带者在右侧rCMA和左侧背侧运动前皮层显示出更强的运动相关活动增加，但仅在运动依赖于内部信号的情况下。此外，在无症状携带者相对于非携带者的内部选择运动的背景下，rCMA的突触活动对基底神经节的活动有更强的影响。我们推断，纹状皮质运动回路的重组反映了克服潜在黑质纹状体功能障碍的代偿努力。
Mutations in the Parkin gene are the most common known single cause of early-onset parkinsonism. It has been shown that asymptomatic carriers with a single mutant allele have latent presynaptic dopaminergic dysfunction in the striatum. Here we used functional MRI to map movement-related neuronal activity during internally selected or externally determined finger movements in 12 asymptomatic carriers of a Parkin mutation and 12 healthy non-carriers. Mean response times were 63 ms shorter during internally selected movements than during externally guided movements (P = 0.003). There were no differences in mean response times between groups (P > 0.2). Compared with externally determined movements, the internal selection of movements led to a stronger activation of rostral motor areas, including the rostral cingulate motor area (rCMA), rostral supplementary motor area, medial and dorsolateral prefrontal cortices. The genotype had a significant impact on movement-related activation patterns. Asymptomatic carriers showed a stronger increase in movement-related activity in the right rCMA and left dorsal premotor cortex, but only if movements relied on internal cues. In addition, synaptic activity in the rCMA had a stronger influence on activity in the basal ganglia in the context of internally selected movements in asymptomatic carriers relative to non-carriers. We infer that this reorganization of striatocortical motor loops reflects a compensatory effort to overcome latent nigrostriatal dysfunction.