Spatiotemporal features of β-γ phase-amplitude coupling in Parkinson's disease derived from scalp EEG
Spatiotemporal features of β-γ phase-amplitude coupling in Parkinson's disease derived from scalp EEG
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DOI：
10.1093/brain/awaa400
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发表时间：
2021-03-03
期刊：
影响因子：
14.5
通讯作者：
Classen, Joseph
中科院分区：
文献类型：
--
作者：
Gong, Ruxue;Wegscheider, Mirko;Classen, Joseph
在帕金森氏症患者的皮层或头皮记录中发现了β和宽带γ活动之间的异常相位振幅耦合。虽然增强的相幅耦合已被提出作为帕金森病的生物标志物，但异常耦合的神经元机制及其与帕金森病运动障碍的关系尚不清楚。为了解决这些问题，我们对19名帕金森病患者和20名年龄和性别匹配的健康对照者的静息时高密度脑电图记录进行了深入分析。利用源重构技术将脑电信号投影到单独的皮层表面，并利用独立分量分析将其分离为时空分量。与健康对照相比，帕金森病患者背外侧前额叶皮层、运动前皮层、初级运动皮层和体感觉皮层的相幅耦合增强，对侧半球与临床更重侧的相幅耦合差异有统计学意义。产生异常相幅耦合的P和y信号不是严格的相相耦合，排除了相幅耦合仅仅反映了循环网络中单个振荡器的异常活动。我们发现来自相同组件的p和y信号与来自不同组件（源自不同的空间位置）的信号之间的耦合存在重要差异。虽然这两种耦合在患者中都异常增强，但根据运动障碍协会统一帕金森病评定量表的第三部分，只有后者与临床运动严重程度相关。在运动前皮层、初级运动皮层和体感觉皮层中发现了这种成分间耦合与帕金森运动症状的相关性，但在背外侧前额叶皮层中没有发现，这表明运动域具有特异性。与对照组相比，患者的相位振幅耦合地形表现出深刻的差异。这些发现表明，首先，帕金森病患者的相幅耦合增强源于参与运动控制的几个大脑区域中不同神经网络之间的耦合。因为这些区域包括体感觉皮层，异常的相位振幅耦合并不仅仅与连接皮层区域与丘脑下核的单突触超直接束有关。其次，只有来自不同成分的β和γ信号之间的耦合似乎具有病理生理意义，这表明打破神经元回路之间异常侧偶联的治疗方法可能比靶向相位-振幅耦合本身更有希望。
Abnormal phase-amplitude coupling between beta and broadband-gamma activities has been identified in recordings from the cortex or scalp of patients with Parkinson's disease. While enhanced phase-amplitude coupling has been proposed as a biomarker of Parkinson's disease, the neuronal mechanisms underlying the abnormal coupling and its relationship to motor impairments in Parkinson's disease remain unclear. To address these issues, we performed an in-depth analysis of high-density EEG recordings at rest in 19 patients with Parkinson's disease and 20 age- and sex-matched healthy control subjects. EEG signals were projected onto the individual cortical surfaces using source reconstruction techniques and separated into spatiotemporal components using independent component analysis. Compared to healthy controls, phase-amplitude coupling of Parkinson's disease patients was enhanced in dorsolateral prefrontal cortex, premotor cortex, primary motor cortex and somatosensory cortex, the difference being statistically significant in the hemisphere contralateral to the clinically more affected side. p and y signals involved in generating abnormal phase-amplitude coupling were not strictly phase-phase coupled, ruling out that phase-amplitude coupling merely reflects the abnormal activity of a single oscillator in a recurrent network. We found important differences for couplings between the p and y signals from identical components as opposed to those from different components (originating from distinct spatial locations). While both couplings were abnormally enhanced in patients, only the latter were correlated with clinical motor severity as indexed by part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale. Correlations with parkinsonian motor symptoms of such inter-component couplings were found in premotor, primary motor and somatosensory cortex, but not in dorsolateral prefrontal cortex, suggesting motor domain specificity. The topography of phase-amplitude coupling demonstrated profound differences in patients compared to controls. These findings suggest, first, that enhanced phase-amplitude coupling in Parkinson's disease patients originates from the coupling between distinct neural networks in several brain regions involved in motor control. Because these regions included the somatosensory cortex, abnormal phase-amplitude coupling is not exclusively tied to the hyperdirect tract connecting cortical regions monosynaptically with the subthalamic nudeus. Second, only the coupling between beta and gamma signals from different components appears to have pathophysiological significance, suggesting that therapeutic approaches breaking the abnormal lateral coupling between neuronal circuits may be more promising than targeting phase-amplitude coupling per se.