Paulsen Jane S, Zimbelman Janice L, Hinton Sean C, Langbehn Douglas R, Leveroni Catherine L, Benjamin Michelle L, Reynolds Norman C, Rao Stephen M
Department of Psychiatry, University of Iowa College of Medicine, Iowa City, USA.
AJNR Am J Neuroradiol. 2004 Nov-Dec;25(10):1715-21.
Functional MR imaging (fMRI) has been used to probe basal ganglia function in people with presymptomatic Huntington's disease (pre-HD). A previous fMRI study in healthy individuals demonstrated activation of the basal ganglia during a time-discrimination task. The current study was designed to examine the relative sensitivity of fMRI compared with that of behavioral testing and morphometric measurements in detecting early neurodegenerative changes related to Huntington's disease (HD).
Pre-HD participants were assigned to two groups based on estimated years to diagnosis of manifest disease: close <12 years and far >or=12 years. Age at disease onset was estimated using a regression equation based on the number of trinucleotide CAG repeats. The time-discrimination task required participants to determine whether a specified interval was shorter or longer than a standard interval of 1200 milliseconds.
Participants in the close group performed more poorly on the time-task discrimination than did control subjects; however, no differences were observed between far participants and control subjects. Similarly, close participants had reduced bilateral caudate volume relative to that of control subjects, whereas far participants did not. On functional imaging, close participants had significantly less activation in subcortical regions (caudate, thalamus) than control subjects; far participants had an intermediate degree of activation. In contrast, far participants had hyperactivation in medial hemispheric structures (anterior cingulate, pre-supplementary motor area) relative to close and control subjects.
Hyperactivation of medial prefrontal regions compensated for reduced subcortical participation during time discrimination in pre-HD. This pattern of brain activation may represent an early neurobiologic marker of neuronal dysfunction.
功能磁共振成像（fMRI）已被用于探究症状前亨廷顿舞蹈病（pre-HD）患者的基底神经节功能。之前一项针对健康个体的fMRI研究表明，在时间辨别任务期间基底神经节会被激活。本研究旨在检验fMRI与行为测试及形态测量相比，在检测与亨廷顿舞蹈病（HD）相关的早期神经退行性变化方面的相对敏感性。
根据预计出现明显疾病的诊断年限，将pre-HD参与者分为两组：接近发病组（<12年）和远期发病组（≥12年）。使用基于三核苷酸CAG重复次数的回归方程估算疾病发病年龄。时间辨别任务要求参与者确定指定间隔比1200毫秒的标准间隔短还是长。
接近发病组参与者在时间任务辨别上的表现比对照组差；然而，远期发病组参与者与对照组之间未观察到差异。同样，接近发病组参与者双侧尾状核体积相对于对照组减小，而远期发病组参与者则没有。在功能成像方面，接近发病组参与者皮质下区域（尾状核、丘脑）的激活明显少于对照组；远期发病组参与者的激活程度处于中间水平。相比之下，相对于接近发病组和对照组参与者，远期发病组参与者内侧半球结构（前扣带回、辅助运动前区）存在过度激活。
内侧前额叶区域的过度激活补偿了pre-HD患者在时间辨别过程中皮质下参与度的降低。这种脑激活模式可能代表神经元功能障碍的早期神经生物学标志物。
