School of Psychology and Psychiatry, Monash University, Clayton, VIC 3800, Australia.
Brain Cogn. 2013 Oct;83(1):80-91. doi: 10.1016/j.bandc.2013.07.004. Epub 2013 Aug 9.
This study aimed to characterize, for the first time, 18 month longitudinal changes in both functional activation and functional connectivity during working memory in premanifest Huntington's disease (pre-HD) and symptomatic HD (symp-HD).
Functional magnetic resonance imaging (fMRI) was used to investigate longitudinal changes in neuronal activity during working memory performance via an N-BACK task (0-BACK and 1-BACK) in 27 pre-HD, 17 symp-HD, and 23 control participants. Whole-brain analysis of activation and region-of-interest analysis of functional connectivity was applied to longitudinal fMRI data collected at baseline and 18 months follow-up.
Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK versus 0-BACK in the lateral and medial prefrontal, anterior cingulate, primary motor, and temporal areas cortically, and caudate and putamen subcortically. Pre-HD far from onset, compared with controls, showed further longitudinal increases in the right and left dorsolateral prefrontal cortex (DLPFC). Longitudinal increased activation in anterior cingulate and medial primary motor areas were associated with disease burden in the pre-HD group. Moreover, in pre-HD increased activation over time in primary motor and putamen regions were associated with average response time during 1-BACK performance. During 1-BACK, functional connectivity between the right DLPFC and posterior parietal, anterior cingulate, and caudate was significantly reduced over 18months only in the pre-HD group.
Longitudinal reductions in connectivity over 18 months may represent an early signature of cortico-cortical and cortico-striatal functional disconnectivity in pre-HD, whereas the concomitant increased cortical and subcortical activation may reflect a compensatory response to the demands for cognitive resources required during task performance. Our findings demonstrate that functional imaging modalities have the potential to serve as sensitive methods for the assessment of cortical and subcortical responses to future treatment measures.
本研究首次旨在描述在无症状亨廷顿病（pre-HD）和有症状亨廷顿病（symp-HD）中，工作记忆期间的功能激活和功能连接的 18 个月纵向变化。
使用功能磁共振成像（fMRI）通过 N-BACK 任务（0-BACK 和 1-BACK）研究 27 名 pre-HD、17 名 symp-HD 和 23 名对照参与者在工作记忆表现期间神经元活动的纵向变化。对基线和 18 个月随访时采集的纵向 fMRI 数据进行全脑激活分析和感兴趣区功能连接分析。
与对照组相比，pre-HD 组在 1-BACK 与 0-BACK 相比时，在外侧和内侧前额叶、前扣带回、初级运动和颞叶皮质以及尾状核和壳核下区显示出明显的纵向激活增加。在 pre-HD 发病前，与对照组相比，右侧和左侧背外侧前额叶皮质（DLPFC）的纵向增加进一步增加。前扣带回和内侧初级运动区的纵向激活增加与 pre-HD 组的疾病负担相关。此外，在 pre-HD 中，随着时间的推移，初级运动和壳核区域的激活增加与 1-BACK 表现期间的平均反应时间相关。在 1-BACK 期间，仅在 pre-HD 组中，右侧 DLPFC 与顶叶后区、前扣带回和尾状核之间的功能连接在 18 个月内显著降低。
18 个月内连接的纵向减少可能代表 pre-HD 中皮质-皮质和皮质-纹状体功能连接中断的早期特征，而同时增加的皮质和皮质下激活可能反映了对任务执行期间所需认知资源的需求的补偿反应。我们的发现表明，功能成像方式有可能成为评估未来治疗措施对皮质和皮质下反应的敏感方法。
