Abstract：
BACKGROUND: Freezing of gait (FOG) is a debilitating symptom of Parkinson\'s disease (PD) characterized by paroxysmal episodes in which patients are unable to step forward. A research priority is identifying cortical changes before freezing in PD-FOG.
METHODS: We tested 19 patients with PD who had been assessed for FOG (n=14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications (\"off\" state) and in the \"on\" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest.
RESULTS: EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n=14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n=5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the \"off\" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas.
CONCLUSIONS: Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of \"unintended stopping.\" These findings may inform approaches to neurorehabilitation of PD-FOG.
METHODS: We tested 19 patients with PD who had been assessed for FOG (n=14 with FOG and 5 without FOG). While seated, patients stepped bilaterally on pedals to progress forward through a virtual hallway while 64-channel EEG was recorded. We assessed cortical activities before and during lower limb motor blocks (LLMB), defined as a break in rhythmic pedaling, and stops, defined as movement cessation following an auditory stop cue. This task was selected because LLMB correlates with FOG severity in PD and allows recording of high-quality EEG. Patients were tested after overnight withdrawal from dopaminergic medications (\"off\" state) and in the \"on\" medications state. EEG source activities were evaluated using individual MRI and standardized low resolution brain electromagnetic tomography (sLORETA). Functional connectivity was evaluated by phase lag index between seeds and pre-defined cortical regions of interest.
RESULTS: EEG source activities for LLMB vs. cued stops localized to right posterior parietal area (Brodmann area 39), lateral premotor area (Brodmann area 6), and inferior frontal gyrus (Brodmann area 47). In these areas, PD-FOG (n=14) increased alpha rhythms (8-12 Hz) before LLMB vs. typical stepping, whereas PD without FOG (n=5) decreased alpha power. Alpha rhythms were linearly correlated with LLMB severity, and the relationship became an inverted U-shape when assessing alpha rhythms as a function of percent time in LLMB in the \"off\" medication state. Right inferior frontal gyrus and supplementary motor area connectivity was observed before LLMB in the beta band (13-30 Hz). This same pattern of connectivity was seen before stops. Dopaminergic medication improved FOG and led to less alpha synchronization and increased functional connections between frontal and parietal areas.
CONCLUSIONS: Right inferior parietofrontal structures are implicated in PD-FOG. The predominant changes were in the alpha rhythm, which increased before LLMB and with LLMB severity. Similar connectivity was observed for LLMB and stops between the right inferior frontal gyrus and supplementary motor area, suggesting that FOG may be a form of \"unintended stopping.\" These findings may inform approaches to neurorehabilitation of PD-FOG.
摘要：
背景：步态冻结（FOG）是帕金森病（PD）的一种衰弱症状，其特征是阵发性发作，患者无法前进。研究的重点是在PD-FOG中冷冻之前确定皮质变化。
方法：我们测试了19例接受FOG评估的PD患者（n=14例有FOG，5例无FOG）。坐下来，在记录64通道EEG时，患者两侧踩着踏板，通过虚拟走廊向前推进。我们评估了下肢运动阻滞（LLMB）之前和期间的皮质活动，定义为有节奏的踩踏中断，并停止，定义为听觉停止提示后的运动停止。之所以选择此任务，是因为LLMB与PD中的FOG严重程度相关，并且可以记录高质量的EEG。在从多巴胺能药物（“关闭”状态）和“开启”药物状态下过夜停药后对患者进行测试。使用单独的MRI和标准化的低分辨率脑电磁断层扫描（sLORETA）评估EEG源活动。通过种子和预定义的感兴趣的皮质区域之间的相位滞后指数评估功能连通性。
结果：LLMB的EEG源活动与位于右后顶叶区域（Brodmann区域39）的提示停止，横向运动前区域（Brodmann区域6），和额下回（布罗德曼区47）。在这些地区,PD-FOG（n=14）在LLMB之前增加α节律（8-12Hz）典型的踏步,而没有FOG的PD（n=5）降低α功率。Alpha节律与LLMB严重程度呈线性相关，在“关闭”药物状态下，当评估作为LLMB百分比时间的函数的alpha节律时，这种关系变成了倒U形。在β波段（13-30Hz）的LLMB之前，观察到右额下回和补充运动区的连通性。在停止之前看到了相同的连接模式。多巴胺能药物改善FOG，并导致α同步减少，额叶和顶叶区域之间的功能连接增加。
结论：右顶下额叶结构与PD-FOG有关。主要的变化是阿尔法节奏，在LLMB之前和LLMB严重性增加。对于右额下回和辅助运动区之间的LLMB和停止观察到类似的连通性，这表明FOG可能是一种“意外停止”的形式。“这些发现可能为PD-FOG的神经康复方法提供信息。
方法：我们测试了19例接受FOG评估的PD患者（n=14例有FOG，5例无FOG）。坐下来，在记录64通道EEG时，患者两侧踩着踏板，通过虚拟走廊向前推进。我们评估了下肢运动阻滞（LLMB）之前和期间的皮质活动，定义为有节奏的踩踏中断，并停止，定义为听觉停止提示后的运动停止。之所以选择此任务，是因为LLMB与PD中的FOG严重程度相关，并且可以记录高质量的EEG。在从多巴胺能药物（“关闭”状态）和“开启”药物状态下过夜停药后对患者进行测试。使用单独的MRI和标准化的低分辨率脑电磁断层扫描（sLORETA）评估EEG源活动。通过种子和预定义的感兴趣的皮质区域之间的相位滞后指数评估功能连通性。
结果：LLMB的EEG源活动与位于右后顶叶区域（Brodmann区域39）的提示停止，横向运动前区域（Brodmann区域6），和额下回（布罗德曼区47）。在这些地区,PD-FOG（n=14）在LLMB之前增加α节律（8-12Hz）典型的踏步,而没有FOG的PD（n=5）降低α功率。Alpha节律与LLMB严重程度呈线性相关，在“关闭”药物状态下，当评估作为LLMB百分比时间的函数的alpha节律时，这种关系变成了倒U形。在β波段（13-30Hz）的LLMB之前，观察到右额下回和补充运动区的连通性。在停止之前看到了相同的连接模式。多巴胺能药物改善FOG，并导致α同步减少，额叶和顶叶区域之间的功能连接增加。
结论：右顶下额叶结构与PD-FOG有关。主要的变化是阿尔法节奏，在LLMB之前和LLMB严重性增加。对于右额下回和辅助运动区之间的LLMB和停止观察到类似的连通性，这表明FOG可能是一种“意外停止”的形式。“这些发现可能为PD-FOG的神经康复方法提供信息。
