Cai Jiayue, Liu Aiping, Wang Yuheng, Tan Sun Nee, Chomiak Taylor, Burt Jacqueline, Camicioli Richard, Hu Bin, McKeown Martin J, Ba Fang
School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China.
Division of Neurology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.
Front Neurosci. 2022 Aug 9;16:930810. doi: 10.3389/fnins.2022.930810. eCollection 2022.
Gait disturbances are critical motor symptoms in Parkinson's disease (PD). The mechanisms of gait impairment in PD are not entirely understood but likely involve changes in the Pedunculopontine Nucleus (PPN), a critical locomotion center, and its associated connections. Exercise is universally accepted as helpful in PD, but the extent and intensity of exercise required for plastic changes are unclear.
Twenty-seven PD subjects participated in a 3-month gait training intervention. Clinical assessments and resting-state functional magnetic resonance imaging were performed at baseline and 3 months after exercise. Functional connectivity of PPN was assessed by combining the methods of partial least squares, conditional dependence and partial correlation. In addition, paired t-tests were used to examine the effect of exercise on PPN functional connectivity and clinical measures, and Pearson's correlation was used to assess the association between altered PPN functional connectivity and clinical measures.
Exercise significantly improved Unified Parkinson's Disease Rating Scale-III (UPDRS-III). A significant increase in right PPN functional connectivity was observed after exercise, which did not correlate with motor improvement. However, the decrease in left PPN functional connectivity significantly correlated with the improvement in UPDRS-III and was linearly related to both number of walks and the duration of walks. In addition, exercise induced a significant increase in the laterality of PPN connectivity strength, which correlated with motor improvement.
PPN functional connectivity is modifiable by walking exercise in both a dose-independent (right PPN and laterality of PPN connectivity strength) and dose-dependent (left PPN) manner. The PPN may contribute to pathological and compensatory processes in PD gait control. The observed gait improvement by walking exercise is most likely due to the reversal of the maladaptive compensatory mechanism. Altered PPN functional connectivity can be a marker for exercise-induced motor improvement in PD.
步态障碍是帕金森病（PD）的关键运动症状。PD 中步态受损的机制尚未完全明确，但可能涉及脑桥脚核（PPN）的变化，PPN 是一个关键的运动中枢及其相关连接。运动对 PD 有益已得到普遍认可，但产生可塑性变化所需的运动程度和强度尚不清楚。
27 名 PD 患者参与了为期 3 个月的步态训练干预。在基线和运动后 3 个月进行临床评估和静息态功能磁共振成像。通过结合偏最小二乘法、条件依赖和偏相关方法评估 PPN 的功能连接性。此外，使用配对 t 检验来检验运动对 PPN 功能连接性和临床指标的影响，并使用 Pearson 相关性分析来评估 PPN 功能连接性改变与临床指标之间的关联。
运动显著改善了统一帕金森病评定量表第三部分（UPDRS-III）。运动后观察到右侧 PPN 功能连接性显著增加，这与运动改善无关。然而，左侧 PPN 功能连接性的降低与 UPDRS-III 的改善显著相关，并且与步行次数和步行持续时间均呈线性相关。此外，运动导致 PPN 连接强度的偏侧性显著增加，这与运动改善相关。
PPN 功能连接性可通过步行运动以剂量非依赖性（右侧 PPN 和 PPN 连接强度的偏侧性）和剂量依赖性（左侧 PPN）方式进行调节。PPN 可能在 PD 步态控制的病理和代偿过程中起作用。观察到的步行运动引起的步态改善最可能是由于适应不良代偿机制的逆转。PPN 功能连接性的改变可能是 PD 中运动诱导的运动改善的一个标志物。
