METHODS: Patients with PD were instructed to walk at a comfortable pace on a mat with pressure sensors. The characterization of cognitive-motor interplay was enhanced by using a gait with a secondary cognitive task (dual-task condition) and a gait without additional tasks (single-task condition). Participants were scanned using 3-T MRI and 123I-ioflupane SPECT.
RESULTS: According to gait characteristics, cluster analysis assisted by a nonlinear dimensionality reduction technique, t-distributed stochastic neighbor embedding, categorized 56 patients with PD into 3 subpopulations. The preserved gait (PG) subgroup (n = 23) showed preserved speed and variability during gait, both with and without additional cognitive load. Compared with the PG subgroup, the mildly impaired gait (MIG) subgroup (n = 16) demonstrated deteriorated gait variability with additional cognitive load and impaired speed and gait variability without additional cognitive load. The severely impaired gait (SIG) subgroup (n = 17) revealed the slowest speed and highest gait variability. In addition, group differences were found in attention/working memory and executive function domains, with the lowest performance in the SIG subgroup than in the PG and MIG subgroups. Using resting-state functional MRI, the SIG subgroup demonstrated lower functional connectivity of the left and right frontoparietal network (FPN) with the caudate than the PG subgroup did (left FPN, d = 1.21, p < 0.001; right FPN, d = 1.05, p = 0.004). Cortical thickness in the FPN and 123I-ioflupane uptake in the striatum did not differ among the 3 subgroups. By contrast, the severity of Ch4 density loss was significantly correlated with the level of functional connectivity degradation of the FPN and caudate (left FPN-caudate, r = 0.27, p = 0.04).
CONCLUSIONS: These findings suggest that the functional connectivity of the FPN with the caudate, as mediated by the cholinergic Ch4 projection system, underlies the compensatory recruitment of attention and executive function for damaged automaticity in gait in patients with PD.
方法:指示患有PD的患者在带有压力传感器的垫子上以舒适的速度行走。通过使用具有次要认知任务的步态(双重任务条件)和没有其他任务的步态(单任务条件),可以增强认知-运动相互作用的表征。使用3-TMRI和123I-碘氟烷SPECT对参与者进行扫描。
结果:根据步态特征,在非线性降维技术的辅助下进行聚类分析,t分布随机邻居嵌入,将56例PD患者分为3个亚群。保留步态(PG)亚组(n=23)在步态期间显示出保留的速度和变异性,有和没有额外的认知负荷。与PG亚组相比,轻度步态受损(MIG)亚组(n=16)表现出伴随额外认知负荷的步态变异性恶化,以及不伴随额外认知负荷的速度和步态变异性受损.严重受损的步态(SIG)亚组(n=17)显示出最慢的速度和最高的步态变异性。此外,在注意力/工作记忆和执行功能域中发现了群体差异,SIG子组的性能低于PG和MIG子组。使用静息状态功能磁共振成像,与PG亚组相比,SIG亚组显示出左右额叶网络(FPN)与尾状的功能连通性较低(左FPN,d=1.21,p<0.001;右FPN,d=1.05,p=0.004)。FPN的皮质厚度和纹状体中123I-碘氟烷的摄取在3个亚组之间没有差异。相比之下,Ch4密度损失的严重程度与FPN和尾状(左FPN-尾状,r=0.27,p=0.04)。
结论:这些研究结果表明,FPN与尾状核的功能性连接,由胆碱能Ch4投射系统介导,这是PD患者步态自律性受损的代偿性注意力和执行功能的基础。