Physiological Analysis Of Involuntary Movements

不随意运动的生理分析

• 批准号: 7143846
• 负责人: MARK A HALLETT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7143846
• 关键词: GABA receptor; Tourette' s syndrome; abnormal involuntary movement; brain mapping; dopamine; drug screening /evaluation; electroencephalography; electromyography; functional magnetic resonance imaging; gamma aminobutyrate; human subject; human therapy evaluation; myoclonus; nervous system disorder chemotherapy; neural information processing; neuroimaging; neuropathology; neuropharmacologic agent; neurophysiology; pathologic process; patient oriented research; positron emission tomography; schizophrenia; sleep disorders; transcranial magnetic stimulation; tremor

The goal of this project is to understand the underlying physiological mechanisms of different involuntary movement disorders. The tools we use include clinical neurophysiological methods such as electroencephalography (EEG), electromyography, and transcranial magnetic stimulation (TMS) and neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Currently active projects in the Section include studies of tremor, tic, and psychogenic movement disorders. New drugs are needed for treatment of essential tremor. Using tremor accelerometry and clinical tremor testing we have shown that 1-octanol, as a single dose, can be safely used (up to 64 mg/kg) and that it significantly reduces tremor. We are planning to study the pharmacokinetics of octanol. We have been approaching the physiology of tics in several ways. We conducted an event related fMRI study in 10 patients with Tourette Syndrome while spontaneously exhibiting a variety of motor and vocal tics. The results of this study indicate that paralimbic and sensory association areas are critically implicated in the generation of tics, similarly to movements triggered internally by unpleasant sensations as has been shown for pain or itching. We are also using blood flow PET to try to define the anatomy for tic generation. In this situation, we are using a sleep state for baseline so that we can have a state largely free of both tics and urge to tic. The analysis of data shows significant activation of bilateral cerebellum and insula during tic release accompanied by activation of structures already known to be involved in tic pathology such as the putamen, supplementary motor area (SMA) and anterior cingulate cortex. We are also studying the pathology of Tourette syndrome with PET using ligand 11C flumazenil to evaluate changes in the distribution and density of inhibitory GABA A receptors. Using BOLD fMRI, we are attempting to characterize the areas of brain activation associated with involuntary urge phenomena such as the infectious nature of yawning. Using a paradigm to assess the timing of conscious events and EEG analysis, we are seeking to understand the timing of cognitive processes related to the conscious awareness of movement preparation and execution. We are investigating the timing of voluntary movement in normal controls as well as in two patient populations--schizophrenic patients and patients with Tourette's syndrome. We have begun to explore the pathophysiology of psychogenic movement disorders including tremor and myoclonus. We have found that prior to psychogenic myoclonus electroencephalographic focal spectral power changes occur similarly to that seen with voluntary movements, signaling that neural substrates active during the pre-execution phase of voluntary and psychogenic movements may be shared. We are initiating a comprehensive psychiatric assessment of these patients. Patients with restless legs syndrome are being studied through an evaluation of the blink reflex as a probe of dopaminergic function. We are interested in the R2 component and how it is affected by auditory and prepulse inhibition when compared with controls. We have conducted a study looking at persons with paroxysmal kinesiogenic dystonia to characterize the condition better clinically. Simultaneously, there are attempts by an extramural collaborator to find the responsible mutated gene. We have begun to explore the pathophysiology of psychogenic movement disorders including tremor and myoclonus. We are doing EEG and neuroimaging studies trying to identify the parts of the brain responsible for movement initiation.

这个项目的目标是了解不同的不自主运动障碍的潜在生理机制。我们使用的工具包括临床神经生理学方法，如脑电图（EEG），肌电图和经颅磁刺激（TMS）以及正电子发射断层扫描（PET）和功能性磁共振成像（fMRI）的神经成像。该科目前正在进行的项目包括震颤、抽搐和心因性运动障碍的研究。 需要新的药物来治疗原发性震颤。使用震颤加速度计和临床震颤测试，我们已经表明，1-辛醇，作为一个单一的剂量，可以安全地使用（高达64毫克/公斤），它显着减少震颤。我们计划研究辛醇的药代动力学。 我们已经从几个方面研究了抽搐的生理学。我们对10例抽动秽语综合征患者进行了事件相关功能磁共振成像研究，同时自发表现出各种运动和发声抽搐。这项研究的结果表明，大脑边缘和感觉关联区在抽搐的产生中起着至关重要的作用，类似于由疼痛或瘙痒引起的不愉快感觉所引发的内部运动。我们还使用血流PET来尝试定义抽搐产生的解剖结构。在这种情况下，我们使用睡眠状态作为基线，这样我们就可以有一个基本上没有抽搐和抽搐冲动的状态。数据分析显示，在抽搐释放过程中，双侧小脑和小脑的显著激活伴随着已知参与抽搐病理的结构的激活，例如壳核、辅助运动区（SMA）和前扣带皮层。我们也正在研究抽动秽语综合征的病理PET使用配体11 C氟马西尼，以评估抑制性GABA A受体的分布和密度的变化。利用BOLD功能磁共振成像，我们试图描述与无意识冲动现象（如打哈欠的传染性）相关的大脑激活区域。 使用一个范例来评估意识事件的时间和EEG分析，我们正在寻求了解与运动准备和执行的意识意识相关的认知过程的时间。我们正在调查正常对照组和两个患者群体--精神分裂症患者和抽动秽语综合征患者的自主运动时间。 我们已经开始探索心因性运动障碍的病理生理学，包括震颤和肌阵挛。我们已经发现，心因性肌阵挛之前，脑电图局灶性频谱功率的变化发生类似的自愿运动，信号，在执行前阶段的自愿和心因性运动的神经基板活动可能是共享的。我们正在对这些病人进行全面的精神评估。 不宁腿综合征患者正在通过评价眨眼反射作为多巴胺能功能的探针进行研究。我们感兴趣的R2组件，以及它是如何受到听觉和前脉冲抑制相比，控制。 我们已经进行了一项研究，观察阵发性运动源性肌张力障碍的人，以更好地描述临床条件。与此同时，一位校外合作者试图找到负责的突变基因。 我们已经开始探索心因性运动障碍的病理生理学，包括震颤和肌阵挛。我们正在做脑电图和神经成像研究，试图确定大脑中负责运动启动的部分。