Fling Brett W, Cohen Rajal G, Mancini Martina, Carpenter Samuel D, Fair Damien A, Nutt John G, Horak Fay B
Department of Neurology, School of Medicine, Oregon Health & Science University, Portland, Oregon, United States of America.
Department of Psychology and Communication Studies, University of Idaho Moscow, Idaho, United States of America.
PLoS One. 2014 Jun 17;9(6):e100291. doi: 10.1371/journal.pone.0100291. eCollection 2014.
Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson's disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG- and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG- patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss of lower-order, automatic control of gait by the basal ganglia.
冻结步态（FoG）是一种短暂的无法启动或维持行走的能力，常伴随晚期帕金森病（PD）出现，并严重损害行动能力。本研究采用多模态神经成像方法，评估有无冻结步态的PD患者在功能和结构运动神经网络上的差异，并将这些发现与冻结步态严重程度的测量指标相关联。26名PD患者和15名年龄匹配的对照者接受了静息态功能磁共振成像和扩散张量成像，以及关于冻结步态的自我报告和临床评估。经过严格的运动校正后，15名PD患者和14名对照参与者可供分析。我们评估了辅助运动区（SMA）与以下每个半球内的运动枢纽之间的功能连接强度：1）丘脑底核（STN）、2）中脑和3）小脑运动区（分别为MLR和CLR）。此外，我们量化了运动枢纽之间的结构连接强度，并评估了其与冻结步态指标的关系。与无冻结步态（FoG-）患者和对照组相比，有冻结步态（FoG+）的患者在SMA与双侧MLR之间以及SMA与左侧CLR之间表现出更强的功能连接。重要的是，SMA与MLR之间更强的功能连接与以下方面呈正相关：i）临床、ii）自我报告以及iii）FoG+患者中冻结严重程度的客观评分，这可能反映了一种适应不良的神经补偿。当前研究结果表明，FoG+患者的运动网络内功能通信发生了重组，即负责步态启动的高级运动皮层（SMA）与MLR和CLR的通信程度比FoG-患者和对照组更高。在FoG+中观察到的连接改变模式可能表明中枢神经系统试图补偿STN与SMA之间连接丧失的尝试失败，并且可能反映了基底神经节对步态的低级自动控制丧失。
