Sintini Irene, Ali Farwa, Stephens Yehkyoung, Clark Heather M, Stierwalt Julie A, Machulda Mary M, Satoh Ryota, Josephs Keith A, Whitwell Jennifer L
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Neuroimage Clin. 2025;45:103727. doi: 10.1016/j.nicl.2024.103727. Epub 2024 Dec 17.
Progressive supranuclear palsy (PSP) can present with different clinical variants which show distinct, but partially overlapping, patterns of neurodegeneration and tau deposition in a network of regions including cerebellar dentate, superior cerebellar peduncle, midbrain, thalamus, basal ganglia, and frontal lobe. We sought to determine whether disruptions in functional connectivity within this PSP network measured using resting-state functional MRI (rs-fMRI) differed between PSP-Richardson's syndrome (PSP-RS) and the cortical and subcortical clinical variants of PSP. Structural MRI and rs-fMRI scans were collected for 36 PSP-RS, 25 PSP-cortical and 34 PSP-subcortical participants who met the Movement Disorder Society PSP clinical criteria. Ninety participants underwent flortaucipir-PET scans. MRIs were processed using CONN Toolbox. Functional connectivity between regions of the PSP network was compared between each PSP group and 83 healthy controls, and between the PSP groups, covarying for age. The effect of flortaucipir uptake and clinical scores on connectivity was assessed. Connectivity was reduced in PSP-RS compared to controls throughout the network, involving cerebellar dentate, midbrain, basal ganglia, thalamus, and frontal regions. Frontal regions showed reduced connectivity to other regions in the network in PSP-cortical, particularly the thalamus, caudate and substantia nigra. Disruptions in connectivity in PSP-subcortical were less pronounced, with the strongest disruption between the pallidum and striatum. There was moderate evidence that elevated subcortical flortaucipir uptake correlated with both increased and reduced connectivity between regions of the PSP network. Lower connectivity within the PSP network correlated with worse performance on clinical tests, including PSP rating scale. Patterns of disrupted functional connectivity revealed both variant-specific and shared disease pathways within the PSP network among PSP clinical variants, providing insight into disease heterogeneity.
进行性核上性麻痹（PSP）可表现为不同的临床变体，这些变体在包括小脑齿状核、小脑上脚、中脑、丘脑、基底神经节和额叶在内的一系列区域网络中呈现出独特但部分重叠的神经退行性变和tau蛋白沉积模式。我们试图确定，使用静息态功能磁共振成像（rs-fMRI）测量的该PSP网络内功能连接的中断在PSP-理查森综合征（PSP-RS）与PSP的皮质和皮质下临床变体之间是否存在差异。为36名符合运动障碍协会PSP临床标准的PSP-RS、25名PSP-皮质型和34名PSP-皮质下型参与者收集了结构MRI和rs-fMRI扫描数据。90名参与者接受了氟代脱氧葡萄糖正电子发射断层显像（flortaucipir-PET）扫描。使用CONN Toolbox对MRI进行处理。比较了每个PSP组与83名健康对照之间以及PSP组之间PSP网络区域之间的功能连接，并对年龄进行了协变量分析。评估了氟代脱氧葡萄糖摄取和临床评分对连接性的影响。与对照组相比，PSP-RS整个网络的连接性降低，涉及小脑齿状核、中脑、基底神经节、丘脑和额叶区域。在PSP-皮质型中，额叶区域与网络中其他区域的连接性降低，尤其是与丘脑、尾状核和黑质的连接。PSP-皮质下型的连接中断不太明显，苍白球和纹状体之间的中断最为强烈。有中等证据表明，皮质下氟代脱氧葡萄糖摄取升高与PSP网络区域之间连接性的增加和降低均相关。PSP网络内较低的连接性与包括PSP评定量表在内的临床测试中较差的表现相关。功能连接中断的模式揭示了PSP临床变体中PSP网络内特定变体和共同的疾病途径，为疾病异质性提供了见解。
