Impaired sequence learning in carriers of the DYT1 dystonia mutation
Impaired sequence learning in carriers of the DYT1 dystonia mutation
复制标题
DOI：
10.1002/ana.10610
复制
发表时间：
2003-07-01
影响因子：
11.2
通讯作者：
Eidelberg, D
中科院分区：
文献类型：
--
作者：
Ghilardi, MF;Carbon, M;Eidelberg, D
先前的正电子发射断层扫描 (PET) 研究表明，DYT1 肌张力障碍突变的非显性携带者表现出异常的静息葡萄糖代谢模式。为了确定这些受试者的运动行为是否受损，我们将 12 名临床上未受影响的 DYT1 携带者与 12 名年龄匹配的对照者的运动和序列学习进行了比较。使用同步 (H2O)-O-15/PET 评估任务执行过程中脑功能的区域差异。我们发现 DYT1 组和对照组的运动表现相似，在每项任务期间测量的运动时间和空间精度没有显着差异。相反，相对于对照组，基因携带者的序列学习能力有所降低（p < 0.01）。运动执行过程中的 PET 成像显示，左侧前运动皮层和右侧辅助运动区基因携带者的激活增加（p < 0.001，未校正），同时小脑后内侧减少。在序列学习过程中，DYT1 携带者左腹侧前额叶皮层和小脑外侧的激活反应增加。这些发现表明，临床上未表现出的 DYT1 携带者存在运动行为和脑功能异常。尽管神经活动的局部增加可能使这些受试者能够正常执行运动，但这种机制可能无法弥补他们在序列学习中的缺陷。
Previous positron emission tomography (PET) studies have shown that nonmanifesting carriers of the DYT1 dystonia mutation express an abnormal pattern of resting glucose metabolism. To determine whether motor behavior is impaired in these subjects, we compared movement and sequence learning in 12 clinically unaffected DYT1 carriers with 12 age-matched controls. Regional differences in brain function during task performance were assessed with simultaneous (H2O)-O-15/PET. We found that motor performance was similar in the DYT1 and control groups, with no significant differences in movement time and spatial accuracy measured during each of the tasks. In contrast, sequence learning was reduced in gene carriers relative to controls (p < 0.01). PET imaging during motor execution showed increased activation in gene carriers (p < 0.001, uncorrected) in the left premotor cortex and right supplementary motor area, with concomitant reduction in the posterior medial cerebellum. During sequence learning, activation responses in DYT1 carriers were increased in the left ventral prefrontal cortex, and lateral cerebellum. These findings suggest that abnormalities in motor behavior and brain function exist in clinically nonmanifesting DYT1 carriers. Although localized increases in neural activity may enable normal movement execution in these subjects, this mechanism may not compensate for their defect in sequence learning.