帕金森病丘脑底核场电位信号多特征提取及药物影响研究

	帕金森病丘脑底核场电位信号多特征提取及药物影响研究
其他题名	The influence of medication on multiple features of subthalamic nucleus local field potentials in Parkinson’s disease
	王亚楠
学位类型	硕士
导师	王守岩
	2015-11
学位授予单位	中国科学院大学
学位专业	机械电子工程
关键词	帕金森病丘脑底核局部场电位信号神经标记物药物治疗
摘要	帕金森病(Parkinson's Disease，PD)是一种常见的神经系统退行性疾病，其震颤、肌肉强直及运动迟缓等运动症状的产生与黑质纹状体内多巴胺的缺失有关，服用多巴胺类药物能够有效抑制这些症状，且药物治疗是帕金森病临床治疗的基础。研究表明帕金森病存在着基底神经节-丘脑-皮层环路神经元异常放电。丘脑底核（Subthalamic Nucleus, STN）神经活动与帕金森病密切相关，其局部场电位（Local Field Potentials, LFPs）信号具有高时间分辨率和高空间分辨率的特点，可提供丰富的神经波动成分信息，反映帕金森病人的脑功能状态。药物治疗作为一种外界刺激会对脑功能状态产生显著影响，该影响可能与帕金森病的治疗机制密切相关。本文从帕金森病患者丘脑底核局部场电位信号入手,研究药物治疗对帕金森病丘脑底核神经波动的影响。通过分析局部场电位的节律性、平衡性及耦合性等局部神经网络特征，研究药物治疗下丘脑底核神经波动的变化，以及这些变化与帕金森病症状改善之间的关系，试图寻找可用于闭环深部脑刺激调控的神经信号生物学标记，并且建立神经波动与帕金森病运动症状之间的桥梁,为寻找更为客观的帕金森病临床评估指标奠定基础。实验采集接受双侧深部脑刺激器植入手术的帕金森病患者在服用多巴胺类药物前后坐姿静止态下丘脑底核局部场电位信号，同时对患者进行肌电监测，筛选出无震颤状态下绝对静止的25 s数据用于后续分析，并收集患者深部脑刺激植入手术前3个月左右服药前后的帕金森病症状评估量表，对场电位的节律性、平衡性及耦合性特征进行分析，并比较药物对其影响。神经活动的节律性包括稳态的节律性和动态节律性,即同步化特征和同步化特征的时间稳定性，分别使用功率谱密度及时变能量的变异系数来量化；使用不同频率成分同步化强度的比值度量神经活动的平衡性；不同频段信号时变能量的互相关系数作为神经活动耦合性的指标。实验主要分为两个部分,首先通过差异性统计分析寻找服药前后局部场电位显著变化的特征，然后通过分析与帕金森病各运动症状间的相关性对特征的意义进行研究。实验结果表明，服药后Theta频段同步化增强、低Beta频段同步化降低，且Theta同步化与肌肉强直和运动迟缓症状呈负相关，低Beta同步化与肌肉强直和运动迟缓呈正相关；Theta和高Gamma同步化的稳定性均显著降低，且Theta同步化稳定性与运动整体症状呈负相关，高Gamma同步化稳定性与运动整体症状呈正相关；（4~10Hz，10~20Hz）间平衡性降低，其与肌肉强直及运动迟缓呈正相关，（12~20Hz，20~38Hz）间平衡性增强，其与震颤呈正相关；药物对（30~38Hz，4~10Hz）（49~55Hz，25~30Hz）（50~60Hz，4~10Hz）（59~65Hz，20-28Hz）等多频段间的耦合性有显著影响，其中只有（59~65Hz，20~28Hz）间的耦合性与肌肉强直呈正相关。丘脑底核局部场电位在药物治疗下多频段节律性、平衡性及耦合性发生变化，这些变化反应了药物作用下帕金森病脑功能状态受药物治疗的影响，其中部分特征与帕金森病震颤、肌肉强直及运动迟缓等运动症状密切相关，这些特征可用于描述神经波动与行为学症状间的关系。本文通过对局部场电位多维特征进行分析，找到了多种与药物治疗相关的神经波动特征，并通过相关分析将其分成运动症状相关和非运动症状相关两类。文中多维度特征的发现将有助于建立基于多特征融合的更为敏感和特异的神经信号生物学标记，为实现脑功能状态判别提供判定指标；为神经波动与帕金森病症状之间建立了桥梁，为帕金森病临床评估的量化提供基础。
其他摘要	Parkinson's disease (PD) is a common nervous system degenerative disease. The development of PD motor symptoms such as tremor, rigidity and bradykinesia is closely related to the lack of dopamine in substantia nigra and striatum. Taking dopaminergic agents to replenish the missing dopamine can effectively suppress the symptoms. Therefore, drug therapy becomes the foundation of clinical treatment to Parkinson's disease. Many studies have showed that the neuron paradoxical discharge in basal ganglion, thalamus and cortex circuit is associated with PD. The local field potentials of subthalamic nucleus (STN) with high temporal and spatial resolutions can provide wealthy information of neural oscillation, and also reflect the brain functional states to some extent. As a kind of stimulation, medication may affect the brain functional states. Furthermore, the influence of medication is relevant to PD’s therapeutic mechanism. This paper analysed the effect of medication on the neural activity in STN base on the local oscillatory network with multi-modal behaviors including rhythm, balancing and coupling behaviors, in order to investigate the relationship between local oscillatory network change and PD motor symptoms with medication. This study aimed to provide quantitative biomarkers for the clinical treatments by medication or deep brain stimulation, and build a bridge between neural activity and PD symptoms. The subthalamic nucleus local field potentials were recorded from 9 patients with Parkinson’s disease undergoing bilateral deep brain stimulator implantation at the states of on and off medication. Resting state signals were monitored by electromyography to make sure there was 25s data without tremor available for analysis. Unified Parkinson’s disease rating scale (UPDRS) score was collected three months before the surgery. The rhythm behaviors including electromyography to make sure there was 25s data without tremor available for analysis. Unified Parkinson’s disease rating scale (UPDRS) score was collected three months before the surgery. The rhythm behaviors including electromyography to make sure there was 25s data without tremor available for analysis. Unified Parkinson’s disease rating scale (UPDRS) score was collected three months before the surgery. The rhythm behaviors including Results of power spectrum analysis demonstrated that low beta band showed de synchronization , and theta band synchronization was increased after taking medication. While both beta and theta band synchronization are related with rigidity and bradykinesia,the results of CV of time-varying power indicated temporal stability of theta and high gamma band synchronization after taking medication. In addition, they are relevant to overall motor symptoms of PD. After taking medication the balance behavior between 4~10Hz and 10~20Hz was decreased, which was related with the rigidity and bradykinesia. On the other hand, balance between 12~20Hz and 20~38Hz was increased, which was related with tremor symptom. Furthermore, the coupling behavior of 30~38Hz and 4~10Hz, 49~55Hz and 25~30Hz, 50~60Hz and 4~10Hz, 59~65Hz and 20~28Hz was affected by medication. However, just coupling behavior of 59~65Hz and 20~28Hz was related to PD symptoms of bradykinesia. Medication affects multiple features of the local oscillatory network of STN. Some of those are closely related with PD motor symptoms. The findings would provide quantitative biomarkers for studying the mechanisms and treatments by medication or deep brain stimulation of Parkinson’s disease.
语种	中文
文献类型	学位论文
条目标识符	http://ir.ciomp.ac.cn/handle/181722/49252
专题	中科院长春光机所知识产出
推荐引用方式 GB/T 7714	王亚楠. 帕金森病丘脑底核场电位信号多特征提取及药物影响研究[D]. 中国科学院大学,2015.

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