Freezing of gait in Parkinson's disease reflects a sudden derangement of locomotor network dynamics
Freezing of gait in Parkinson's disease reflects a sudden derangement of locomotor network dynamics
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DOI：
10.1093/brain/awz141
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发表时间：
2019-07-01
期刊：
影响因子：
14.5
通讯作者：
Isaias, Ioannis U.
中科院分区：
文献类型：
--
作者：
Pozzi, Nicolo G.;Canessa, Andrea;Isaias, Ioannis U.
步态冻结是帕金森病的一种致残症状，会导致阵发性无法有效迈步。潜在的病理生理学最近已转向功能失调的脊髓上运动网络，但持续步态冻结期间的实际网络紊乱尚不清楚。我们使用一种新型深部脑刺激装置，对七名患有帕金森病的自由活动受试者研究了皮层和底丘脑核（运动网络的两个主要节点）之间的通信，该装置允许在手术后几个月从长期植入的电极按需记录底丘脑神经活动。 （有效）行走和持续步态冻结期间的多部位神经生理学记录与运动学测量和个体分子脑成像研究相结合。患者在与日常生活挑战非常相似的监督环境中行走。我们发现，在（有效）步行过程中，皮层和丘脑底核在低频段（4-13 Hz）同步。相比之下，每名患者的步态冻结的特点是半球皮质-底丘脑低频解耦，纹状体多巴胺能神经支配较少。相关的是，这种解耦在从正常（有效）步行到步态冻结的过渡过程中已经很明显，并且在冻结期间得以维持，并随着有效步行模式的恢复而得到解决。这是解码帕金森病运动网络化处理的第一个证据，并表明步态冻结是一种与功能失调的皮质-皮质下通讯相关的“回路病”。帕金森病步态冻结的成功治疗方法应旨在直接针对神经网络动力学紊乱。
Freezing of gait is a disabling symptom of Parkinson's disease that causes a paroxysmal inability to generate effective stepping. The underlying pathophysiology has recently migrated towards a dysfunctional supraspinal locomotor network, but the actual network derangements during ongoing gait freezing are unknown. We investigated the communication between the cortex and the subthalamic nucleus, two main nodes of the locomotor network, in seven freely-moving subjects with Parkinson's disease with a novel deep brain stimulation device, which allows on-demand recording of subthalamic neural activity from the chronically-implanted electrodes months after the surgical procedure. Multisite neurophysiological recordings during (effective) walking and ongoing gait freezing were combined with kinematic measurements and individual molecular brain imaging studies. Patients walked in a supervised environment closely resembling everyday life challenges. We found that during (effective) walking, the cortex and subthalamic nucleus were synchronized in a low frequency band (4-13 Hz). In contrast, gait freezing was characterized in every patient by low frequency cortical-subthalamic decoupling in the hemisphere with less striatal dopaminergic innervation. Of relevance, this decoupling was already evident at the transition from normal (effective) walking into gait freezing, was maintained during the freezing episode, and resolved with recovery of the effective walking pattern. This is the first evidence for a decoding of the networked processing of locomotion in Parkinson's disease and suggests that freezing of gait is a 'circuitopathy' related to a dysfunctional cortical-subcortical communication. A successful therapeutic approach for gait freezing in Parkinson's disease should aim at directly targeting derangements of neural network dynamics.