NEUROIMAGING, NEUROPSYCHIATRY, AND COGNITIVE FUNCTIONING

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们将改进现有的功能磁共振成像(FMRI)范式，以评估具有亨廷顿病(HD)突变的症状前患者在涉及精细运动任务的内隐学习任务时的基底节活动。我们假设(A)涉及运动序列内隐学习的fMRI任务将把HD症状前阶段的个体与年龄、性别、利手和不携带HD基因的种族匹配的个体区分开来，以及(B)壳核的激活水平和内隐学习的程度之间存在相关性。这项工作将直接解决功能性的问题，而不是结构性的基底节异常在HD中开始，这可能是一个很好的指标，何时应该开始治疗(特别是假设治疗可能是昂贵的或有不良的副作用)。该项目的数据在未来治疗试验的设计中也将是有价值的。这样的治疗试验目前正在对有症状的HD患者进行，可以合理地假设，在有症状的人群中确定第一个成功的治疗后，将立即对HD基因的症状前携带者进行试验。我们之前对有症状和症状前个体的纵向MRI研究提供了初步数据，表明基底节的体积MRI测量可以作为此类治疗试验的极佳结果指标，特别是在症状前人群中，对他们来说，无法使用症状严重程度的测量。我们推测，功能磁共振测量可能对HD症状前阶段基底节的最早变化更敏感。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We will refine existing functional MRI (fMRI) paradigms to assess basal ganglia activity in presymptomatic persons with the Huntington's Disease (HD) mutation during tasks involving implicit learning of fine motor tasks. We hypothesize (a) that fMRI tasks involving implicit learning of motor sequences will differentiate individuals at the presymptomatic stages of HD from age, sex, handedness and race- matched individuals who do not carry the HD gene and (b) that correlations will exist between activation level of the putamen and extent of implicit learning. This work will directly address the question of when functional, as opposed to structural basal ganglia abnormalities begin in HD, which may be a good indicator of when treatment should begin (especially assuming that the treatment may be costly or have undesirable side effects). Data from this project will also be valuable in the design of future treatment trials. Such treatment trials are currently underway with symptomatic HD patients, and it is reasonable to assume that trials with presymptomatic carriers of the HD gene will occur immediately following the identification of the first successful treatment within the symptomatic population. Our previous longitudinal MRI studies with symptomatic and presymptomatic individuals provide preliminary data suggesting that volumetric MRI measures of basal ganglia may serve as excellent outcome measures for such treatment trials, especially within the presymptomatic population for whom measures of symptom severity cannot be used. We hypothesize that functional MRI measures may be even more sensitive to the earliest changes in basal ganglia in the presymptomatic stages in HD.