Asymmetric pedunculopontine network connectivity in parkinsonian patients with freezing of gait
Asymmetric pedunculopontine network connectivity in parkinsonian patients with freezing of gait
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DOI：
10.1093/brain/awt172
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发表时间：
2013-08-01
期刊：
影响因子：
14.5
通讯作者：
Horak, Fay B.
中科院分区：
文献类型：
--
作者：
Fling, Brett W.;Cohen, Rajal G.;Horak, Fay B.
步态冻结是帕金森氏病中最令人衰弱的症状之一，因为它会导致福尔斯跌倒并降低活动性和生活质量。脚桥核是中脑运动区的主要核团之一，其神经元与步骤启动前的预期姿势调整以及步骤本身相关，因此它可能是耦合姿势和步态以避免冻结的关键。由于步态和姿势障碍的冻结与额叶病变和额叶功能障碍（如执行功能）有关，我们假设冻结与中脑运动区域和内侧额叶皮质之间的连接中断有关。我们使用扩散张量成像来量化帕金森病患者的脚桥核的结构连接与冻结的步态，没有冻结，和健康的年龄匹配的控制。我们还纳入了行为任务，以衡量步态冻结的严重程度，量化步态指标，并评估执行认知功能，以确定执行功能障碍的组间差异是否与脚桥核结构网络连接有关。使用来自脚桥核的种子区域，我们能够描绘出脊髓、小脑、脚桥核、皮质下和额叶/前额叶皮质区域之间的白色物质连接。目前的研究是第一个证明在结构连接的差异，已确定的运动路径的患者冻结步态。我们报告了脚桥核与小脑、丘脑和额叶皮质多个区域的连接减少。此外，这些结构差异仅在步态冻结患者的右半球中观察到。最后，我们表明，更多的左半球偏侧的脚桥核束体积，性能较差的认知任务，需要启动适当的行动和/或抑制不适当的行动，特别是在冻结的患者。这些结果支持的观点，冻结的步态是密切相关的结构缺陷，在右半球的运动网络涉及前额叶皮层区参与执行抑制功能。
Freezing of gait is one of the most debilitating symptoms in Parkinson's disease as it causes falls and reduces mobility and quality of life. The pedunculopontine nucleus is one of the major nuclei of the mesencephalic locomotor region and has neurons related to anticipatory postural adjustments preceding step initiation as well as to the step itself, thus it may be critical for coupling posture and gait to avoid freezing. Because freezing of gait and postural impairments have been related to frontal lesions and frontal dysfunction such as executive function, we hypothesized that freezing is associated with disrupted connectivity between midbrain locomotor regions and medial frontal cortex. We used diffusion tensor imaging to quantify structural connectivity of the pedunculopontine nucleus in patients with Parkinson's disease with freezing of gait, without freezing, and healthy age-matched controls. We also included behavioural tasks to gauge severity of freezing of gait, quantify gait metrics, and assess executive cognitive functions to determine whether between-group differences in executive dysfunction were related to pedunculopontine nucleus structural network connectivity. Using seed regions from the pedunculopontine nucleus, we were able to delineate white matter connections between the spinal cord, cerebellum, pedunculopontine nucleus, subcortical and frontal/prefrontal cortical regions. The current study is the first to demonstrate differences in structural connectivity of the identified locomotor pathway in patients with freezing of gait. We report reduced connectivity of the pedunculopontine nucleus with the cerebellum, thalamus and multiple regions of the frontal cortex. Moreover, these structural differences were observed solely in the right hemisphere of patients with freezing of gait. Finally, we show that the more left hemisphere-lateralized the pedunculopontine nucleus tract volume, the poorer the performance on cognitive tasks requiring the initiation of appropriate actions and/or the inhibition of inappropriate actions, specifically within patients with freezing. These results support the notion that freezing of gait is strongly related to structural deficits in the right hemisphere's locomotor network involving prefrontal cortical areas involved in executive inhibition function.