Basal Ganglia Shape Analysis and Circuitry in Huntington's Disease

描述(申请人提供)：亨廷顿病(HD)是一种进行性、致命性、神经退行性疾病，具有运动障碍、精神特征和认知能力下降。神经变性是区域性的异质性，优先丢失纹状体中棘神经元，但在其他区域有显著萎缩。这就引出了这样一个问题：这种区域变性模式是否与电路有关，反映了受影响神经元的解剖连接，或者相反，是多灶性的。为了解决这个问题，我们将对基底节进行统计形状分析，并检查连接萎缩区域和受影响皮质区域的白质结构。我们假设在选定的皮质下区域会有异质性萎缩，形状分析可能会在总体体积显著变化之前及早发现一些局部性变化。我们假设，区域性苍白球萎缩与特定的局部基底节连接相关，但区域性纹状体萎缩并不完全与区域性皮质萎缩预测的连接相关。我们还将对白质结构进行补充分析。具体地说，目标1将对351名患有和不患有HD前驱症状的受试者进行横断面统计形状分析(尾状核、壳核、丘脑、海马体、伏隔核和苍白球)；目标2将对351名受试者进行2个时间点的特定皮质下灰质区域(如上所述)的纵向形状分析；以及目标3将对白质结构进行分析，以确定受影响最严重的纹状体区域是否接受来自皮质最受影响的区域的投射，以及苍白球受影响最严重的区域是否接受来自纹状体最受影响区域的投射。

DESCRIPTION (provided by applicant): Huntington disease (HD) is a progressive, fatal, neurodegenerative disease, with movement disorder, psychiatric features, and cognitive decline. The neurodegeneration is regionally heterogeneous with preferential loss of striatal medium spiny neurons, but with significant atrophy in other regions. This leads to the question whether this pattern of regional degeneration is circuit related, reflecting the anatomic connections of the affected neurons, or by contrast is multifocal. To address this question, we will perform statistical shape analysis of basal ganglia and examine white matter structures connecting atrophied regions with affected cortical regions. We hypothesize that there will be heterogeneous atrophy in selected subcortical regions, and that shape analysis may detect some localized changes early, before overall volumes change significantly. We hypothesize that regional globus pallidus atrophy will correlate with specific local basal ganglia connections, but that regional striatal atrophy will not entirely correlate with connections predicted by regional cortical atrophy. We will also perform complementary analysis of white matter structures. Specifically Aim 1 will perform cross- sectional statistical shape analysis (caudate, putamen, thalamus, hippocampus, nucleus accumbens and globus pallidus) in 351 subjects with and without prodromal HD; Aim 2 will perform longitudinal shape analysis on specific subcortical gray matter regions (as listed above) for 351 subjects with scans at 2 time points; and Aim 3 will perform analysis of white matter structures in to determine whether the regions of striatum most affected receive projections from the regions of cortex most affected, and whether the regions of globus pallidus most affected receive projections from the regions of striatum most affected.