NEUROIMAGING, NEUROPSYCHIATRY, AND COGNITIVE FUNCTIONING

点击翻译按钮获取中文摘要

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.