Increased cerebellar activation during sequence learning in DYT1 carriers: an equiperformance study
Increased cerebellar activation during sequence learning in DYT1 carriers: an equiperformance study
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DOI：
10.1093/brain/awm243
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发表时间：
2008-01-01
期刊：
影响因子：
14.5
通讯作者：
Eidelberg, David
中科院分区：
文献类型：
--
作者：
Carbon, Maren;Ghilardi, Maria Felice;Eidelberg, David
我们已经发现，运动序列学习和相关的大脑激活受损的DYT 1缺失肌张力障碍的非显着（nm）载体。在本研究中，我们使用了一个试错序列学习任务，结合等效研究设计，以确定支持nmDYT 1突变携带者序列学习的神经基质。六nmDYT 1突变携带者和六名对照受试者进行了扫描（H2O）-O-15 PET在试错指导，运动学控制的运动序列学习任务和匹配的运动执行任务的性能。对照组的年龄和表现相匹配。使用统计参数映射（SPM 99）进行PET数据分析。尽管表现在匹配的水平上，nmDYT 1突变携带者相对于年龄匹配的对照组过度激活了外侧小脑和右侧颞下皮层（P < 0.001）。相反，他们在双侧背外侧前额叶皮层、左前扣带回和背侧运动前皮层显示出相对激活缺陷（P < 0.001）。在目标学习过程中小脑的显著代偿参与与我们先前在nmDYT 1突变携带者中的序列学习实验一致。与突变携带者相比，正常人只有在面临更高的任务难度时才使用双侧小脑激活和显著的前额叶双侧化。nmDYT 1突变携带者缺乏这些前额叶区域的募集，这些前额叶区域依赖于皮质-纹状体-苍白球-丘脑皮质（CSPTC）环路内的调节。相反，它们仅通过小脑激活来补偿。这一观察结果与最近的证据一致，即肌张力障碍中CSPTC网络内的结构/功能关系受损，可能发生在神经发育的基础上。由于额-纹状体连接的改变，无法招募适当的新皮层区域，这可能导致了向小脑处理的转移。
We have found that motor sequence learning and related brain activation is impaired in non-manifesting (nm) carriers of the DYT1 deletion for dystonia. In the present study we used a trial-and-error sequence-learning task in conjunction with an equiperformance study design to identify the neural substrates that support sequence learning in nmDYT1 mutation carriers. Six nmDYT1 mutation carriers and six control subjects were scanned with (H2O)-O-15 PET during the performance of a trial-and-error guided, kinematically controlled motor sequence learning task and a matched motor execution task. Controls were matched for age and performance. PET data analysis was performed using statistical parametric mapping (SPM99). Although performing at matched levels, nmDYT1 mutation carriers overactivated the lateral cerebellum and the right inferotemporal cortex relative to age-matched controls (P < 0.001). In contrast, they showed relative activation deficits in the dorsolateral prefrontal cortex bilaterally, as well as in the left anterior cingulate and the dorsal premotor cortex (P < 0.001). Prominent compensatory involvement of the cerebellum during target learning is consistent with our prior sequence-learning experiments in nmDYT1 mutation carriers. Contrasting to mutation carriers, normals used bilateral cerebellar activation in conjunction with a prominent prefrontal bilateralization only when confronted with a much higher task difficulty. nmDYT1 mutation carriers lack recruitment of these prefrontal regions that depend on modulation within the cortico-striato-pallido-thalamocortical (CSPTC) loops. Instead, they compensate solely using cerebellar activation. This observation is in keeping with recent evidence of impaired structure/function relationships within CSPTC networks in dystonia perhaps occurring on a neurodevelopmental basis. The inability to recruit the appropriate set of neocortical areas because of altered fronto-striatal connectivity may have led to the shift to cerebellar processing.