Miranda-Domínguez Óscar, Ragothaman Anjanibhargavi, Hermosillo Robert, Feczko Eric, Morris Rosie, Carlson-Kuhta Patricia, Nutt John G, Mancini Martina, Fair Damien, Horak Fay B
Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Department of Biomedical Engineering, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Neuroscience. 2020 Sep 1;443:44-58. doi: 10.1016/j.neuroscience.2020.06.036. Epub 2020 Jul 3.
Freezing of gait (FoG) is a brief, episodic absence or marked reduction of forward progression of the feet, despite the intention to walk, that is common in people with Parkinson's disease (PD). We hypothesized that not only motor, but higher level cognitive and attention areas may be impaired in freezers. In this study, we aimed to characterize differences in cortical and subcortical functional connectivity specific to FoG. We examined resting state neuroimaging and objective measures of FoG severity and gait from 103 individuals (28 PD + FoG, 36 PD - FoG and 39 healthy controls). Inertial sensors were used to quantify freezing severity and gait. Groups with and without FoG were matched on age, disease severity, cognitive status, and levodopa medication. MRI data was processed using surface-based registration. High-quality imaging data were used to characterize differences in connectivity specific to FoG using a pre-defined set of Regions of Interest (ROIs) and validated using whole-brain connectivity analysis. Associations between functional connectivity and objective measures of FoG were determined via predictive modeling using hold-out cross validation. We found that connectivity between the left globus pallidus (GP) and left somatosensory cortex and between two brain areas in the default and insular/vestibular networks exhibited significant differences specific to FoG and were also strong and significant predictors of FoG severity. Our findings suggest that the interplay among motor, default and vestibular areas of the left cortex are critical in the pathology of FoG.
冻结步态（FoG）是一种短暂的、发作性的双脚向前行进缺失或明显减少，尽管有行走意图，在帕金森病（PD）患者中很常见。我们假设，不仅运动区域，而且更高层次的认知和注意力区域在冻结步态患者中可能也会受损。在本研究中，我们旨在描述特定于冻结步态的皮质和皮质下功能连接差异。我们检查了103名个体（28名PD+FoG、36名PD-FoG和39名健康对照）的静息态神经影像以及冻结步态严重程度和步态的客观测量指标。使用惯性传感器量化冻结严重程度和步态。有和没有冻结步态的组在年龄、疾病严重程度、认知状态和左旋多巴用药方面进行了匹配。MRI数据使用基于表面的配准进行处理。高质量成像数据用于使用预定义的感兴趣区域（ROI）集描述特定于冻结步态的连接差异，并通过全脑连接分析进行验证。通过使用留出交叉验证的预测模型确定功能连接与冻结步态客观测量指标之间的关联。我们发现，左侧苍白球（GP）与左侧体感皮层之间以及默认和岛叶/前庭网络中的两个脑区之间的连接表现出特定于冻结步态的显著差异，并且也是冻结步态严重程度的强有力且显著的预测指标。我们的研究结果表明，左侧皮层的运动、默认和前庭区域之间的相互作用在冻结步态的病理过程中至关重要。
